Novel quinoxaline derivatives of 2, 3-diphenylquinoxaline-6-carbaldehyde and 4, 4′-(6-methylquinoxaline-2,3-diyl)bis(N,N-diphenylaniline): Synthesis, structural, DFT-computational, molecular docking, antibacterial, antioxidant, and anticancer studies

Journal of Molecular Structure 1248 (2022) 131418

Contents lists available at ScienceDirect

Journal of Molecular Structure

journal homepage: www.elsevier.com/locate/molstr

Novel quinoxaline derivatives of 2, 3-diphenylquinoxaline-6-

ꢀ

carbaldehyde and 4, 4 -(6-methylquinoxaline-2,3-diyl)bis

(N,N-diphenylaniline): Synthesis, structural, DFT-computational,

molecular docking, antibacterial, antioxidant, and anticancer studies

J Irshad Ahamed^h,∗, G.R. Ramkumaar^a, P. Kamalarajan^b, K. Narendran^c, M.F. Valan^d,

T. Sundareswaran^e, T.A. Sundaravadivel^f, B. Venkatadri^g, S. Bharathi^h

^aDepartment of Physics, C. Kandaswami Naidu College for Men, Anna Nagar East, Tamil Nadu, India

^bDepartment of Chemistry, R.M.D Engineering College, Kavaraipettai, Tamil Nadu 601206, India

^cDepartment of Chemistry, Saveetha Engineering College, Thandalam, Chennai 602105, India

^dDepartment of Chemistry, IFE (Loyola Institute of Frontier Energy), Loyola College, University of Madras, Nungambakkam, Chennai, Tamil Nadu, 600034,

India

^eDepartment of Physics, RMK College of Engineering and Technology, RSM Nagar, Puduvoyal, Tamil Nadu 601206, India

^fDepartment of Mechanical, R.M.D Engineering College, Kavaraipettai, Tamil Nadu 601206, India

^gDepartment of Plant Biology & Biotechnology, Loyola College (Autonomous), Chennai - 600 034, Tamil Nadu, India. (University of Madras)

^hDepartment of chemistry. (SHIFT – II), C. Kandaswami Naidu College for Men, Anna Nagar East, Chennai, Tamil Nadu 600102, India

a r t i c l e i n f o

a b s t r a c t

ꢀ

Article history:

The quinoxaline derivatives of 2, 3-diphenylquinoxaline-6-carbaldehyde (DPQC) and 4, 4 -(6-

methylquinoxaline-2,3-diyl)bis(N,N-diphenylaniline) (MDBD) were synthesized using direct condensation

methods, and various spectral analysis were characterized by experimental and ab initio Density func-

tional theory (DFT) theoretical methods at the B3LYP level with 6–311++G(d,p) basis sets were used

for the different spectrum analysis, which included UV-Visible, Fourier-transform infrared spectroscopy

(FTIR), and ¹H and ¹³C nuclear magnetic resonance (NMR) chemical shifts. Furthermore, for these title

molecules, Nonlinear Optical (NLO) was utilized to compute ﬁrst-order hyperpolarizability (β) and Mulli-

gan population analysis was performed. The ESI-Mass spectrum analysis was performed for these quinox-

aline derivatives. In this study, title molecules of DPQC and MDBD were tested for in vitro antibacterial,

antioxidant, and anticancer properties which exhibited enhanced biological activities. In particular, the

title molecule MDBD gave enhanced anticancer activity at the lowest concentration of 125 μg/mL against

human liver cancer (HepG2) cell lines, as well as potent bactericidal activity with a maximum of (19.5

1.0 mm) at 2.5 μg/mL against Yersinia enterocolitica (MTCC 840). In an (H₂O₂) scavenging study, MDBD

revealed potent antioxidant activity (64.21%). The DPPH radical scavenging antioxidant activity of MDBD

was discovered at (67.48 %) concentration at 500 μg/mL. The best binding energy between anticancer

target protein, speciﬁcally c-Met-kinase (hepatocyte growth factor; PDB ID: 3F66) and DPQC and MDBD

compounds, were determined using in silico molecular docking. The auto dock software provided supe-

rior results for the title compound MDBD, which exhibited a higher ligand-receptor interaction energy

value of -10.8 (kcal/mol) against 3F66 protein and a 0.01187 μM inhibition constant (ki) with (active site

A) presented amino acids such as A: ARG1086, A: MET1211, A: VAL1092, A: ALA1226, A: ALA1108, A:

MET1211. Further, studies are warranted to explore their promising anticancer and other pharmacological

and biochemical properties.

Received 29 June 2021

Revised 30 August 2021

Accepted 31 August 2021

Available online 3 September 2021

Keywords:

New quinoxaline derivatives DPQC and

MDBD

Spectral characterisation

DFT computational

In vitro Anticancer

Molecular docking

1. Introduction

Cancer is the main cause of morbidity and mortality world-

wide, which developed because of the unregulated increase in

malignant cells which can spread to different organ systems.

Liver cancer is one of the main predominant diseases important

∗

Corresponding author.

E-mail address: irshad@loyolacollege.edu (J.I. Ahamed).

https://doi.org/10.1016/j.molstruc.2021.131418

J.I. Ahamed, G.R. Ramkumaar, P. Kamalarajan et al.

Journal of Molecular Structure 1248 (2022) 131418

for mortality in humans [1]. Quinoxaline is an essential hetero-

cyclic nucleus created via the combination of two types of aro-

matic rings, which include benzene plus pyrazine (additionally

known as benzopyrazine) [2,3]. The broad range of biological ac-

tivities, including the antitumor activity of quinoxaline deriva-

tives, is known and well documented in the literature [4,5]. The

activity of quinoxalines as antitumor agents also showed potent

and selective inhibition of human tyrosine kinase (TRK) in the

liver cancer HepG2 [6]. N-(4-methyl-2-nitrophenyl)-2-(3-methyl-2-

oxoquinoxalin-1(2H)-yl) acetamide has been reported as a poten-

tial antioxidant activity [7]. Antioxidant studies are important ow-

ing to their capability to stop disease development by reducing

the damage caused by free radical oxidative stress in a patient [8].

Even if they started enhanced anticancer agents in the last thirty

years, they have severe side effects from chemotherapy treatment

and severe health problems, leading to death sometimes. Cancer

remains a life-threatening sickness due to the shortage of valuable

anticancer drugs and additionally creates effects of chemotherapy

[9]. Therefore, efforts are still needed to increase great anticancer-

causing agents to deal with most cancers successfully. The chemi-

cal compounds from the heterocyclic class play an essential role in

modern drug discovery by structural modiﬁcation to develop vari-

ous compounds.

mental analyser (India). The Elemental (CHNS/O) analysis speciﬁed

that the calculated and found values were within the acceptable

limits ( 0.4%). Reactions were observed using means of TLC utiliz-

ing precoated plates (Merck, India). Column chromatographic sep-

aration was done using silica gel with a mesh of 60–120.

2.3. Synthesis

2.3.1. General synthesis of novel quinoxaline derivatives are described

in (Scheme 1) for dpqc and mdbd compounds

The different 1, 2- diamines such as 3,4-diaminobenzaldehyde

and 4-methylbenzene-1,2-diamine 2 g, (18.49 mmol) in 20 mL

of methanol, in addition to 3.8

g of different 1, 2-diketones

such as benzil and 1,2-bis(4-(diphenylamino)phenyl)ethane-1,2-

dione (18.49 mmol) were further added to the mixture. Then use

a magnetic stirrer to stir the chemical mixture at room temper-

ature vigorously. The progress of the reaction was monitored by

thin-layer chromatography (TLC). The ﬁnal product was quenched

with water (10 mL) and ethyl acetate (EtOAc) (20 mL). The organic

layer within the chemical mixture was isolated and dried out over

anhydrous Na₂SO₄to give a crude product. The product becomes

isolated and puriﬁed using 60–120 mesh silica gel column chro-

matography using EtOAc 2:8 Hexane ratios.

The search for a brand new quinoxaline agent for most can-

cer remedies is

a crucial device within medicinal chemistry.

2.4. Experimental data

In our current research work, the novel quinoxaline derivatives

ꢀ

of 2,3-diphenylquinoxaline-6-carbaldehyde (DPQC) and 4, 4 -(6-

2.4.1. 2, 3-diphenylquinoxaline-6-carbaldehyde dpqc

methylquinoxaline-2,3-diyl)bis(N,N-diphenylaniline) (MDBD) have

been recognized to behave as anticancer agents for human

(HepG2) liver cancer cell lines and also completed the different

spectroscopic evaluations by experimental and Density Function

Theory (DFT) calculation with B3LYP/ 6–311++G (d,p) level. These

quinoxaline derivatives are cost-effective and their initial materials

are readily available. As quinoxaline moiety-containing molecules

exhibit diverse organic signiﬁcance, this study was interested in

synthesizing the diverse quinoxaline derivatives and examining

their anticancer effects utilizing in vitro and in silico approaches.

Yield: 70 %; Light yellow; mp: 131- 132˚C; IR (KBr, ν, cm⁻¹):

3437 cm⁻¹(OH stretching vibration), 3053, 3028, 2854 cm⁻¹(C-

H stretching vibrations), 1618, 1483, 1444, 1344 cm⁻¹(Aromatic

(C=C) stretching vibrations), 1201, 1138, 1058 (H-C-C bending vi-

brations), 1022, 979, 833, 773, 700, 545 cm⁻¹(H-C-C-C torsion

vibrations), and 592 cm⁻¹(H-C-C bending vibrations); UV(λ_max

,

nm): 251 nm (π → π^∗) and 360 nm (n→ π^∗); ¹H NMR (400 MHz,

CDCl₃): δ 7.26–7.33(m, 6H) 7.46–7.49 (m, 4H), 8.18- 8.19 (d, J=2 Hz,

2H), 8.57 (s, 1H), 10.19 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): 126.77,

128.40, 129.32, 129.47, 129.82, 129.91, 130.46, 134.76, 137.06,

138.46, 140.86, 144.22, 154.78, 155.66, 191.36; Elemental Analysis

calcd % for C₂₁H₁₄N₂O: C, 81.27; H, 4.55; N, 9.03; O, 5.16; Found

%: C, 81.19; H, ₊4.48; N, 9.01; O, 5.08; MS (ESI) for C₂₁H₁₄N₂O: m/z

2. Materials and methods

2.1. Chemicals and reagents

311.40 [M+H]

.

In this study, the chemicals and reagents including ben-

ꢀ

2.4.2. 4, 4 -(6-methylquinoxaline-2,3-diyl)bis(N,N-diphenylaniline)

mdbd

zil,

1,2-bis(4-(diphenylamino)phenyl)ethane-1,2-dione,

3,4-

diaminobenzaldehyde, 4-methylbenzene-1,2-diamine, and MeOH

(Sigma Aldrich, USA), Silica gel with a mesh of 60–120 (Merck,

India), the pre-covered aluminium sheet of silica gel G/UV-254 of

0.2 mm thickness (Merck, Germany) were used for the synthesis

of quinoxaline derivatives.

Yield: 73%; Dark yellow; mp: 222–224˚C;IR (KBr, ν, cm⁻¹):

3243, 3129 cm⁻¹(C-H stretching vibrations), 3004 cm⁻¹(C-

H

asymmetric methyl stretching vibration), 1672, 1607, 1117,

1084cm⁻¹(C=C stretching vibrations), 1417cm⁻¹(C-N stretching

vibration), 1368, 1228 cm⁻¹(H-C-C bending vibrations), 973, 902,

804, 703cm-1 (H-C-C-C torsion vibrations), 653cm⁻¹(C-C-C bend-

ing vibration); UV (λ_max, nm): 314nm(π → π^∗), 371, 470nm(n→

π^∗); ¹H NMR (400 MHz, CDCl₃): δ 2.50 (s, 3H), 6.93–6.96 (m,

4H), 7.09–7.10 (d, J = 1.2 Hz, 8H), 7.25–7.31 (m, 12H), 7.58–7.60

(dd, J = 1.2, 1.2 Hz, 1H), 7.90–7.91 (d, J = 1.6 Hz, 1H), 8.03–

8.04 (d, J = 5.6 Hz, 4H), 8.28–8.30 (d, J = 6 Hz, 1H); ¹³C NMR

(100 MHz, CDCl₃): δ 21.68, 122.90, 124.87, 126.26, 126.36, 128.86,

129.79, 129.95, 131.62, 132.41, 140.11, 140.80, 141.24, 145.42, 147.06,

153.52, 154.22; Elemental Analysis calcd % for C₄₅H₃₄N₄: C, 85.68;

H, 5.43; N, 8.88; Found %: C, ₊85.51; H, 5.34; N, 8.76; MS (ESI) for

2.2. Spectral characterization

The synthesized compounds were recorded by the Fourier

transform infrared (FT-IR) spectrum of the molecule was recorded

employing a Perkin Elmer spectrometer ﬁtted with a KBr beam

splitter at around 4000–500 cm⁻¹with methanol solvent. The

spectral measurements were completed by the Sophisticated An-

alytical Instrumentation Facility (SAIF), IIT, and Madras, India.

The UV-Visible absorption spectra were taken on an Analytikjena

specord 250 spectrophotometer. The NMR spectra (¹H and ¹³C)

were recorded on Bruker Avance (400 MHz and 100 MHz) in CDCl₃

solvent. The chemical shift value is conﬁrmed in δ (ppm), and

the coupling constant (J) is reported in Hz, and tetramethylsilane

(Me4Si) is an internal standard. The mass spectrometry was done

on a total ion chromatography (TIC) spectrometer. Elemental anal-

ysis was completed on the PerkinElmer CHNS/O 2400 series II ele-

C₄₅H₃₄N₄: m/z 631.73 [M+H]

.

2.5. Computational details

The density functional theory has achieved tremendous signif-

icance in quantum chemical computation. The present research

2

J.I. Ahamed, G.R. Ramkumaar, P. Kamalarajan et al.

Journal of Molecular Structure 1248 (2022) 131418

exploration was performed with the B3LYP (Beckee-3- Lee-Yang-

Parr) method, (Gaussian 09 program) package [10] as well as in-

cluded the 6–311++G (d,p) basis set. In the DFT study, the ab-initio

method of molecular calculating properties has recently been en-

hanced [1 1 ]. Initially, the geometry was optimized, followed by the

calculation of geometrical parameters and the vibrational assign-

ments. To avoid the systematic errors caused by basis set incom-

pleteness, negligence of electron correlation and vibrational anhar-

monicity, a general scaling factor of 0.961was used to scale the

computed wavenumbers. Additionally, the computed vibrational

frequencies were revealed through the potential energy distribu-

tion (PED) investigation of all the fundamental vibration modes

reported by the Vibrational Energy Distribution Analysis (VEDA)

[12,13] program. The isotropic shielding values were used to cal-

culate the isotropic chemical shifts (δ) for tetramethylsilane (TMS).

The UV–visible spectra and excited state dipole moment were cal-

culated by the B3LYP method of the time-dependant DFT (TD-DFT)

using a 6–311++G (d, p) basis set based on the optimized struc-

ture [14–16]. The Frontier molecular orbital energies (FMOs) [1 7 ],

Mulliken’s population analysis and molecular electrostatic poten-

tial calculations were carried out and the results are discussed.

The molecular structures were visualized with the help of Gauss

View [18]. The Gauss Sum 3.0 program has been used to ob-

tain calculated FT-IR images [19]. The NLO properties of DPQC

and MDBD like dipole moment (μ), polarizability (

࢞

α) and ﬁrst-

order hyperpolarizability (β) were carried out by the Gaussian 09

modelling package [20]. The ¹H and ¹³C NMR isotropic shielding

was computed using the GIAO method [21,22] and standardized

parameters attained using the B3LYP/6–31G++ (d,p) technique.

δ_iso(X) = σ_TMS(X)- σ_iso(X), where δ_isoisotropic chemical shift plus

σ_isoisotropic shielding.

hydrogen peroxide scavenging.

Hydrogen peroxide scavenging %

=

A − A /A × 100

( )

(

)

0

1

0

Where, A₀is the absorbence of the control, and A₁is the ab-

sorbence of the sample.

The 1,1-diphenyl-2-picrylhydrazine (DPPH) method was utilized

to analyse the antioxidant potential of synthetic compounds based

on scavenging free radicals. In this process, 0.1 mM ethanol DPPH

was prepared and added to the solution of quinoxaline derivatives.

The different concentrations of (DPQC) and (MDBD) range from

100 to 500 μg/ml. It was then incubated for 30 minutes and the

absorbence at 517 nm was assessed via a Beckman spectropho-

tometer. After incubation, the discolouration was calculated using

an accurate blank of 517 nm. Protect from light for 30 minutes at

30 °C in the dark. Assessments were made in triplicate. D-ascorbic

acid was employed as the standard. The DPPH was absorbed at

517 nm, and its reduced concentration used in antioxidant activ-

ity. The following formula measures the percentage of free radical

scavenging activity of the quinoxaline derivatives.

1 − −A_sample− A_blank

A_control

Scavenging % =

× 100

Here, ethanol (3 mL) with the solution sample (0.1 ml) has utilized

as the blank, and 3 ml of DPPH solution with EtOH (0.1 ml) was

utilized as the negative control.

2.8. In vitro anticancer activity

The liver cancer (HepG2) cell line was served to test the anti-

cancer activity of the compounds (DPQC) and (MDBD). Cells were

cultured and maintained in Minimal Essential Media (MEM) (Hi-

Media, India) supplemented with 10% foetal bovine serum (FBS)

(Cistron Labs), Trypsin, MTT (methyl thiazolyl diphenyl-tetrazolium

bromide), and dimethylsulfoxide (DMSO) (Himedia, India). The

(HepG2) cells were incubated at 37 °C in a 5% CO₂atmosphere;

they were regularly subcultured and maintained in 2% MEM. A

conﬂuent monolayer of HepG2 cells was trypsinized and sus-

pended in 10% MEM. 100μL of cell suspension was transferred to

96 well plates followed by 10% MEM was added and the plate

was incubated at 37 °C in a 5% CO₂environment. Various con-

centrations of molecules were prepared as 100 μg/mL, 50 μg/mL,

25 μg/mL, 12.5 μg/mL, 6.25 μg/mL, 3.125 μg/mL, 1.56 μg/mL and

0.78 μg/mL and transferred to the 96 well plates. Finally, 100 μL of

2% MEM was added. The morphological changes of (HepG2) cells

were monitored every 24 h for three days and ﬁnally, the changes

were noted after 72 h of the period. The highest concentration that

did not show cellular toxicity was measured as the maximum non-

toxic concentration of the compound. The cytotoxicity concentra-

tion was approved using the MTT (3-(4, 5-dimethylthiazol-2-YL)-2,

5-diphenyltetrazolium bromide) assay. In this assay, after 72 h of

incubation of 96 well plates, 20 μL of MTT solution (5 mg/mL) was

further added to all the wells and the plate was inculpated at 37 °C

with 5% CO₂for 4 hrs. After 4 hours of incubation, the medium

presented in the plate was carefully removed without disturbing

the cell monolayer. Finally, a volume of 120 μL of DMSO was added

to the wells to dissolve the formazan crystals and read at 510 nm

and 650 nm. The formula used to calculate the percentage of cell

viability was the percentage of cell viability = treated x 100 %/un-

treated.

2.6. In vitro antibacterial activity

The gram-positive microbes Staphylococcus aureus (MTTC 3615),

Enterococcus faecalis (MTCC 439), and the gram-negative bacte-

ria Yersinia enterocolitica (MTCC 840) and Proteus mirabilis (MTCC

1771) from the American type cell culture reference bacterial strain

(ATCC) were exploited for biological analysis with antibacterial test

assays. The Gram-positive bacteria cultures were grown selectively

on Nutrient broth (pH 7.0), whereas Mueller–Hinton broth (pH 7.0)

was used for culturing Gram-negative bacteria. The cultures were

incubated at 37 °C for 24 h in a rotator shaker. After a necessary

period of incubation, the bacterial cultures (1.5 × 108 CFU/mL)

were swabbed onto sterile Mueller Hinton agar plates. The syn-

thesized quinoxaline derivatives of (25 mL) (DPQC and MDBD)

were transferred to sterile discs (6 mm) and allowed to soak for

10–15 min. With the aid of tweezers dipped in ethanol, the disks

were aseptically transferred to the plates seeded with the respec-

tive pathogens, ﬂamed, and incubated at 37 °C for 24 hours. After

24 hours, the zone of inhibition (mm) formed by the combination

of an organic compound was measured relative to the pathogenic

bacteria index. Streptomycin and an appropriate disk immersion

solvent were used as positive and negative controls, correspond-

ingly. The experiments were completed in triplicate [23].

2.7. In vitro antioxidant activity (H₂O₂and dpph radical scavenging

activity)

The antioxidant property was evaluated using an H₂O₂scav-

enging assay. The title molecules (DPQC) and (MDBD) at different

concentrations from 100 to 1000 μg/mL prepared in ethanol were

added to 0.6 mL of H₂O₂solution. After 15 min of incubation, the

absorbence of the reaction mixture was read at 230 nm. The blank

solution includes H₂O₂solution without any compound. The H₂O₂

scavenging activity of synthesized compounds was measured by

2.9. Molecular docking

Human c-Met-Kinase (PDB code: 3F66) complex with quinox-

aline inhibitor was chosen as a protein target for docking investi-

˚

gations. The X-ray diffraction resolution of 3F66 was 1.4 A. [24],

and all molecular docking calculations were performed on Auto

3

J.I. Ahamed, G.R. Ramkumaar, P. Kamalarajan et al.

Journal of Molecular Structure 1248 (2022) 131418

Scheme 1. A synthetic method for quinoxaline derivatives DPQC and MDBD.

Dock-Vina software. Co-crystallized ligands, water, and co-factors

were removed before preparing the protein for docking. The Auto

Dock Tools (ADT) graphical user interface is used to calculate Koll-

man’s charge and polar hydrogen. The Lamarck Genetic Algorithm

(LGA) function of Auto Dock software is used in the docking pro-

cess [25]. In Silico, molecular docking investigations were ﬁnished

by Autodock4.2. Docking analysis was accomplished with the ﬂex-

ible ligand and the rigid receptors. The x, y, z size grid box size

values are 126 × 90 × 126, and the grid box centre x, y, z values

3.2. Molecular geometry

Figs. and shows the optimized structure of the ti-

2

3

tle compounds DPQC and MDBD. Table S1-S4 (Supporting in-

formation) presents their bond lengths and bond angles com-

puted using an optimized structure basis set of 6–311G++ (d,

p) by the DFT method. The minimum energies optimized for

the structure of title molecule DPQC is calculated by the HF/6–

311G++ (d, p) and B3LYP/6–311G++ (d, p), with their values of

-986.778 a.u. and - 993.424 a.u. The energy difference value is

-6.65a.u., whereas the title compound MDBD HF/6–311G++(d,p)

and B3LYP/6–311G++(d,p) minimum energy values are -1940.973

a.u. and -1953.819a.u. with their energy difference value of -12.85

a.u. The novel compound MDBD has shown more energy difference

than DPQC.

˚

are -12.08 x -22.198 × 28.788 with 0.542 A grid spacing at the lo-

cation of binding for the 3F66- Protein. The newly synthesized or-

ganic molecules (DPQC) and (MDBD) ligand structures were drawn

by ChemDraw 12.0 software. The synthesized structure of the 2D

compound is converted to mol format and then converted to 3D.

Auto Dock uses the framework for the docking process [25]; all

these ligands are puriﬁed and obtained through the selected twist

tree using the Auto Dock ligand tool, selecting the torsion tree-

choose root, and torsion tree-detect root. The ﬁnal puriﬁed ligand

is stored through the opening in pdbqt format for further use in

molecular docking studies. Use Discovery Studio software [26] to

perform visualization results.

3.3. Atomic charges

The charge distribution mainly inﬂuences the vibration spec-

trum of the molecule. The total atomic charges of the title com-

pounds DPQC and MDBD were obtained by the methods of

Mulliken [29] and NBO using HF/6–311G++(d,p) and B3LYP/6–

311G++(d,p). The theoretical level is shown in Figs. S1 and

S2 (Supporting information). Total atomic charge values were

achieved by Mulliken population investigation and natural charges

were discovered by natural bond orbital analysis. The charge dis-

tribution is according to the linear combination of atomic orbitals

and thus the wave function of the molecule. All hydrogen atoms

have positive Mulliken charge values.

3. Result and discussion

3.1. Chemistry

The novel derivatives of quinoxaline such as from DPQC and

MDBD were achieved using direct condensation reaction between

1, 2-dicarbonyl (1a-1b) and 1,2-diamine (2a-2b) with the solvent

MeOH 3 in the condition of mild acidity without using any cata-

lyst [27,28]. The complete reaction was given in Scheme 1, which

obtained ﬁnal products with a signiﬁcant yield percentage of 70%-

73%. We explored the inﬂuence of electronic components of 1,2-

diamine on the reaction results. It has been observed that 1,2-

diamine bearing an electron-donating group (-Me) on the benzene

ring, e.g. 4-methylbenzene-1,2-diamine (2b) with 1,2-dicarbonyl

and the related product MDBD, was synthesized in excellent yields.

However, the occurrence of an electron-withdrawing group in the

benzene ring decreased the reactivity of the substrate. Some bio-

logically essential compounds are shown in Fig. 1.

The molecule of the DPQC has atomic charges for the hy-

drogen atom that range from HF/6–311G++ (d, p) of 0.228 to

0.205, whereas B3LYP/6–311G++(d,p) ranges from 0.150 to 0.131.

Because of polarization, the charges change with the basis set. For

example, the charge of N14 atom values is -0.437 for B3LYP/6–

311G++ (d,p) and -0.568 for HF/6–311G++ (d, p). The charge of

N15 atom values is -0.439 for B3LYP/6–311G++(d,p) and -0.576 for

HF/6–311G++ (d, p). Finally, the O38 atom values are -0.393 for

B3LYP/6–311G++(d,p) and -0.522 for HF/6–311G++(d,p), as given

in Table S5 (Supporting information). Table S5 concluded that the

DPQC molecule presented nitrogen and oxygen atoms are exhib-

4

J.I. Ahamed, G.R. Ramkumaar, P. Kamalarajan et al.

Journal of Molecular Structure 1248 (2022) 131418

Fig. 1. Biologically important compounds of Quinoxaline.

Fig. 2. Optimized structure of the title compound DPQC.

ited as a substantial negative charge, which is a donor atom. The

C12, C13, C16, C17, and C36 hydrogen atoms were exhibited posi-

tive charges, which is an acceptor atom.

synthesized compounds, with their geometry positioned at accu-

rate local minima of the potential energy surface. The calculated

wavenumbers are normally superior to the corresponding experi-

mental ones because of electron correlation consequences and in-

adequate basis set deﬁciencies. Therefore, to enhance the calcu-

lated values, the discrepancy between experimental and theory is

eliminated by computing a harmonic correction explicitly, through

initiating a scalar ﬁeld, using scaling of the computed wavenum-

bers with the right scaling factor [31–33].

The molecule of the MDBD and its atomic charges for hydro-

gen atom HF/6–311G++ (d,p) is 0.241 to 0.229, wherein B3LYP/6–

311G++ (d, p) ranges from 0.144 to 0.094. Because of polariza-

tion, the charges of N13 atom values is -0.430 for B3LYP/6–311G++

(d, p) and -0.604 for HF/6–311G++ (d, p), N14 atom values is -

0.431 for B3LYP/6–311G++(d,p) and -0.591 for HF/6–311G++ (d,

p), N38 atom values is -0.722 for B3LYP/6–311G++ (d, p) and -

1.103 for HF/6–311G++ (d, p). Finally, the N39 atom values are -

0.713 for B3LYP/6–311G++ (d, p) and -1.103 for HF/6–311G++ (d,

p), as given in Table S6 (Supporting information). Table S6 con-

cluded that the MDBD molecule contained nitrogen atoms with a

signiﬁcant negative charge, indicating that they were donor atoms.

The C5, C11, C12, C15, C16, and C40 hydrogen atoms were exhibited

as a positive charge, an acceptor atom.

The calculated wavenumbers (scaled), observed and assign-

ments of FT-IR bands for these two synthesized title molecules are

given in Table S7 and S8 (Supporting information), and comparison

between calculated and observed wavenumbers FT-IR are shown in

Fig. 4 for DPQC and Fig. 5 for MDBD. The calculated FT-IR images

have been demonstrated by the Gauss Sum 3.0 program [19]. As

detected from the correlation graphs, the FT-IR correlation coeﬃ-

cient of DPQC and MDBD (CC) R²values are 0.99494 and 0.99947

at the B3LYP/6–311G++(d,p) level. The computed and experimen-

tal FT-IR correlation coeﬃcient spectrum images were revealed in

Fig. S3 for DPQC and Fig. S4 for MDBD. The computed frequencies

match the experimental FT-IR values well. The following vibration

modes of these two new title molecules were discussed.

3.4. Vibrational analysis

The vibration level of the identiﬁed compounds, especially

DPQC and MDBD, is achieved by the DFT level (B3LYP), which

is a way to approach the compound vibration level [30]. These

molecules have been given 108 for DPQC and 243 for MDBD by

positive value modes of vibrations for the conﬁrmation of current

In our current research work, the title molecule DPQC exper-

imental FT-IR (O-H) stretching vibration assigned at 3437cm⁻¹

(mode number 108) with

a PED contribution value of 96%,

5

J.I. Ahamed, G.R. Ramkumaar, P. Kamalarajan et al.

Journal of Molecular Structure 1248 (2022) 131418

Fig. 3. Optimized structure of the title compound MDBD.

Fig. 5. Experimental and Theoretical vibrational spectra of (MDBD).

Fig. 4. Experimental and Theoretical vibrational spectra of (DPQC).

115) are also related to C-H stretching and coincide well with the

calculated frequency values of 3205, 3095, and 2976cm⁻¹with a

79%, 87%, and 99% PED contribution. The title molecule MDBD ex-

perimental C-H stretching vibration detected in the range of 3243

and 3129cm⁻¹with (mode numbers of 242 and 213) are also re-

lated to C-H stretching and coincides a good deal with the cal-

culated frequency values of 3239 and 3193cm⁻¹with a 16%, and

which is perfectly matched with the computed vibrational band

at 3241cm⁻¹, respectively. According to the literature [34,35]. The

aromatic C-H stretching vibrations occur. The substituent’s nature

never affects the bands in this region [36]. The compound DPQC

experimental C-H stretching vibrations obtained in the range of

3053, 3028, and 2854cm⁻¹with (mode numbers of 98, 97, and

6

J.I. Ahamed, G.R. Ramkumaar, P. Kamalarajan et al.

Journal of Molecular Structure 1248 (2022) 131418

13% PED contribution, respectively, as per the literature [37]. Sev-

eral bending vibrations, including β HCC, were observed in the

1563 to 125cm⁻¹range [38]. In our current analysis, the com-

pound DPQC experimental FT-IR bending β HCC vibrations were

discovered at 1201, 1138, 1058, and 592cm⁻¹with a PED contri-

bution value of 15, 13, 15, and 47%. The compound MDBD ex-

perimental FT-IR bending β HCC vibrations are revealed at 1368

and 1228cm⁻¹with a PED contribution value of 49 and 16%. Fur-

thermore, various β CCC bending and τ HCCC torsion vibrations

were achieved in DPQC and MDBD compounds, which have been

extensively studied [39–41]. The compound MDBD C-H stretching

in pure (CH₃) methyl stretching vibration was obtained experi-

mentally at 3004cm⁻¹with a mode number of 210. This is also

reasoned to methyl stretching and coincides well with the calcu-

lated frequency values of 3038cm⁻¹with an 89% PED contribution.

These frequency values were intimately in concord with the same

modes in literature [42–44]. The compound DPQC experimental

wavenumbers at 1618, 1483, and 1444cm^{− 1}observed in the FT-IR

spectrum were assigned to C=C stretching vibrations (mode num-

bers of 89, 81, and 80) PED contribution values of 17, 63, and

51% in the current work. The compound MDBD experimental FT-IR

show C=C stretching vibrations at 1672, 1607, 1117, and 1084cm⁻¹

with a PED contribution value of 28, 17, 25, and 14%, respectively

(mode numbers of 209, 199, 136, and 133). These frequency val-

ues were closely in agreement with the same modes in literature

[45,46]. These two title molecules have achieved excellent concord

with the calculated data given in Tables S7 and S8. The MDBD title

compound experimental wavenumber was obtained at 1417 cm⁻¹

for C-N stretching vibrations. The theoretical scaled wavenumber

was found at 1485cm⁻¹with a mode number of 181 for C-N

stretching vibrations with a PED contribution value of 22%, respec-

tively. The suitable vibration ranges were obtained in the literature

[20]. This amine group raises the reactivity of the linked aromatic

ring and acts as a wonderful neurotransmitter due to its electron-

donating character.

The DPQC and MDBD molecules experimental absorption wave-

lengths (energies) and computed electronic values, such as absorp-

tion wavelength (λ), energy gap (E), oscillator strength (f), and

assignments of electronic transitions are mentioned in Table 1.

The band gap energy was estimated by the E = hc/λ formula.

Here, h and c are constant; λ is the cut-off wavelength [52,53].

Table 1 shows the calculated and experimental wavelengths from

absorption using methanol as a solvent, the % contribution from

each transition, transition energies, and oscillator strength com-

puted at the B3LYP/6–311G++ (d,p) level for DPQC and MDBD in

the gas phase.

3.6. Frontier molecular orbitals (FMOs) analysis

The orbits (LUMO-Lowest Unoccupied Molecular Orbital) and

(HOMO-Highest Occupied Molecular Orbital) are used for the cal-

culation of band gap energy and structures stability. The com-

pounds with a large HOMO and LUMO energy gap are often con-

sidered hard, whereas compounds with a small energy gap are soft

and much more reactive [55]. The computational method results

are shown in Table S9 (Supporting information), which was esti-

mated by HOMO-LUMO energies, energy gap (ꢀE), ionization po-

tential (I), electron aﬃnity (A), absolute electro-negative (χ), and

softness (S) of the DPQC and MDBD molecules. I = − E_HOMOand

A = − E_LUMO, respectively, where I and A are the ionization po-

tentials and electron aﬃnities. In this inspection, the relations be-

tween the DPQC molecule of E_HOMOand E_LUMOare -6.2613 (eV)

and -2.4165 (eV), as well as the relations between MDBD molecule

of E_HOMOand E_LUMO,are -4.8438 (eV) and -1, 7226 (eV) shown

in Fig. 6a and Fig. 7a also show FMOs, where the positive phase

is revealed in red and the negative phase is revealed in green,

and these images showed the occurrence of intramolecular charge

transfer between the DPQC molecule and the MDBD molecule. In

this research, these compounds were shown to have a low band

gap energy value of LUMO-HOMO (Gap (eV) = 3.8448) for the

DPQC molecule and (Gap (eV) = 3.1212) for the MDBD molecule.

This low energy gap indicates charge transfer inside the com-

pound. The stable structure is identical to the band gap of bioac-

tive molecules [56]. Fig. 6a and Fig. 7a suggest that the ioniza-

tion potential value of I = 6.2613 (eV) for the DPQC molecule and

I = 4.8438 (eV) for MDBD molecules are required to eliminate an

electron from the HOMO.

3.5. Ultraviolet-Visible spectral analysis

The absorption spectroscopy of many_∗organic molecules is

based on transitions π → π^∗and n→ π in the UV-Visible re-

gion [47–49]. The UV-Visible spectral analysis was performed to

understand the electronic transitions of the quinoxaline deriva-

tives of 2, 3-diphenylquinoxaline-6-carbaldehyde (DPQC) and 4,

The lower value of electron aﬃnity A = 2.4165 (eV) for the

DPQC molecule and A = 1.7226 (eV) for the MDBD molecule shows

that these two compounds have accepted electrons for reaction.

As a result of having LUMO and HOMO, molecular energy values,

electronegativity, chemical hardness, and other values can be es-

timated by the following formula. χ = I+A/2 (Electronegativity),

μ = -(I+A)/2 (Chemical potential), η = I-A/2 (Chemical hardness),

S=1/2η (chemical softness), and ω=μ²/2η (Electrophilicity index).

The Gauss-sum 3.0 program [19] was employed to simulate the

density of states (DOS) spectrum, which provides a visual repre-

sentation of captured orbitals, virtual orbitals, HOMO and LUMO

energy levels, and band gap of the DPQC and MDBD molecules. The

green and red lines in the DOS spectrum imply occupied and vir-

tual orbitals, respectively. Fig. 6b and Fig. 7b show the DOS spec-

trum of the DPQC molecule and MDBD molecule, respectively.

ꢀ

4 -(6-methylquinoxaline-2,3-diyl)bis (N,N-diphenylaniline) (MDBD)

molecules. The UV-Visible spectrum was theoretically calculated by

a 6–311++G(d,p) basis set for the gas phase. The experimental ab-

sorption spectra of the DPQC and MDBD molecules were recorded

using methanol as a solvent. The overlap of experimental and the-

oretical calculated UV-Visible spectra was presented in Figs. S5 and

S6 (Supporting information).

In the UV–Vis spectrum of compound DPQC, only two bands

are shown at 251 nm and 360 nm. The experimental values of

251 nm and 360 nm correlate with DFT/B3LYP/6–311++G(d,p)

calculated values of 230.31 nm and 354.74 nm, respectively, at-

tributed to HOMO-2→LUMO+2 and HOMO-4→LUMO, which have

electronic transition contribution values of 35% and 75%. The elec-

tronic transitions in DPQC are due to π → π^∗and n→ π^∗tran-

sitions. In the compound MDBD, only three bands are shown at

314 nm, 371 nm, and 470 nm. The experimental values of 314 nm,

371 nm, and 470 nm correlate with DFT/B3LYP/6–311++G(d,p) cal-

culated values at 308.53 nm, 352.10 nm, and 450.05 nm, respec-

tively, attributed to HOMO→LUMO+3, HOMO-1→LUMO+1, and

HOMO →LUMO, which have electronic transition contribution val-

ues of 52%, 36%, and 98%. The electronic transitions in MDBD are

due to π → π^∗and n→ π^∗transitions [50,51].

3.7. Molecular electrostatic potentials (MEP)

The molecular electrostatic potential (MEP) uses colour grad-

ing to depict molecule shapes, size, and electrostatic potential.

The MEPs map and contour plots are valuable tools for evaluating

molecular structures and their physicochemical properties, as well

as drugs [57]. It provides information on a molecule’s chemical re-

activity. The electrophilic or nucleophilic properties are explained

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J.I. Ahamed, G.R. Ramkumaar, P. Kamalarajan et al.

Journal of Molecular Structure 1248 (2022) 131418

Table 1

Theoretical and experimental electronic transition parameters of DPQC and MDBD using a TD-DFT/6–311G++(d,p) method in gas phase and their assignments.

Experimental Theoretical Transitions with % of contributions

Molecules

Transition

λ

_max(nm) Band gap (eV) λ_max(nm) Oscillator strength (f) Assignment [54]

Band gap (eV)

DPQC

π → π^∗

251

360

314

371

470

4.941

3.445

3.940

3.3424

2.6383

230.31

354.74

308.53

352.1

5.3834

3.4951

4.0186

3.5213

2.7549

0.0213

0.001

HOMO-2 → LUMO+2 (35%)

HOMO - 4 → LUMO (75%)

HOMO → LUMO +3 (52%)

HOMO-1 → LUMO+1 (36%)

HOMO → LUMO (98%)

∗

n→ π

MDBD

π → π^∗

0.2586

0.1411

0.2357

∗

n→ π

450.05

Fig. 6. (a) The frontier molecular orbitals of the DPQC molecule. (b) Density of

States spectrum of the DPQC molecule.

Fig. 7. (a) The frontier molecular orbitals of the MDBD molecule. (b) Density of

States spectrum of the MDBD molecule.

(C=O) shows red colours in Fig. 8 and the MDBD compound with

the nitrogen groups N13 and N14 shows red colours in Fig. 9, in-

dicating that the compound negative regions (nucleophilic reactive

sites) are areas that easily interact with proteins for biological ac-

tivity. The hydrogen atoms in DPQC and MDBD compounds are

coloured blue, indicating an electrophilic reactive site, and yellow,

indicating a lower electrostatic potential. The diagram of the MEP

illustrates the electrostatic potential for decreasing compound sur-

faces based on red > orange > yellow > blue [59,60], the following

spectrum of colours.

using the electrostatic potential created surrounding a molecule via

the distribution of charges [58].

Figs 8 and 9 show the DPQC and MDBD title compounds MEPs

map generated by the optimized ﬁgure using the Gauss View 5.0

software. Different colours show the diverse values of the electro-

static potential: red denotes the highest negative electrostatic po-

tential, blue denotes positive electrostatic potential, and green de-

notes the portion of zero potential. The bulk of the light green re-

gion of the MEP surface seems like a possibility between the two

extremes of red and dark blue. The negative regions of molecu-

lar electrostatic potential indicate that the assessed electron den-

sity in the molecule attracts the proton (red shade). The repulsion

of protons by atomic nuclei is represented by the positive electro-

static potential (shades of blue). The MEP map conﬁrms that the

negative potential areas are around oxygen and nitrogen, while the

positive potential areas are around hydrogen atoms, as per these

estimated outcomes. The compound DPQC with the carbonyl group

3.8. Nonlinear optical properties

The polarizability values will determine the NLO properties

[61] and the Nonlinear Optical properties (NLO) activity values of

linear polarizability (α), total molecular dipole moment (μ), and

ﬁrst-order hyperpolarizability (β). The anisotropy of the polariz-

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J.I. Ahamed, G.R. Ramkumaar, P. Kamalarajan et al.

Journal of Molecular Structure 1248 (2022) 131418

Fig. 8. Molecular Electrostatic Potential (MEP) of DPQC.

Fig. 9. Molecular Electrostatic Potential (MEP) of MDBD.

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J.I. Ahamed, G.R. Ramkumaar, P. Kamalarajan et al.

Journal of Molecular Structure 1248 (2022) 131418

Fig. 10. NMR graphical representation of molecule DPQC.

ability (ꢀα) is computed using the B3LYP/6–311G++ (d,p) ba-

sis set from Gaussian 09 W [62]. The μ, α, and β quantities in

conditions of x, y, and z components of DPQC and MDBD were

listed in Tables S10 and S11 (Supporting Information). Hyperpo-

larizability is extremely sensitive to the basic positions and lev-

els employed by theoretical methods [63,64]. Urea is commonly

used to investigate the properties of an NLO compound. Thus, the

most frequently used threshold material, urea, was employed. The

computed investigated molecule for the ﬁrst order hyperpolariz-

ability values is 6.734 × 10⁻³⁰esu for the DPQC molecule and

5.800 × 10⁻³⁰esu for the MDBD molecule. These hyperpolarizabil-

ity values are much greater and more signiﬁcant than the value of

urea (βo = 0.372 × 10⁻³⁰esu) [65]. The total dipole moment of

the DPQC value of (μ=4.5504D) and MDBD value of (μ=1.3886D).

These molecules dipole moments are also larger than the value of

urea (μ=0.988D) [66]. Hence, DPQC and MDBD molecules have ex-

hibited superior NLO properties.

a correlation graph of the title compounds DPQC and MDBD have

shown in Figs. S11 to S14 (Supporting Information), which gives

supported to the calculations. As demonstrated from the graph,

the correlation coeﬃcient (CC) R²values of 0.97578 in (¹³C NMR),

0.9788 in (¹H NMR) for DPQC, and (CC) R²values of 0.9949 in (¹³

C

NMR), 0.9729 in (¹H NMR) for MDBD spectra. The simulated chem-

ical shift (DFT) values are generally closed with the experimental

spectra. The DFT/B3LYP/6–311G++(d,p) ¹H and ¹³C NMR graphical

representation of molecules DPQC and MDBD were shown in Fig.

10 and Fig. 1 1 .

The Aromatic ring protons have a chemical shift in the region of

6.5–8.0 ppm, and also provide downﬁeld signals in ¹H NMR spec-

tra [69,70]. In our title molecule, DPQC proton ¹H NMR spectrum

is observed multiplet (Ar-H) signals from the chemical shift val-

ues at δ 7.331, 7.261, 7.336, and 7.263 ppm for protons H8, H9,

H26, and H27 were located in the benzene group, δ 7.485, 7.488,

7.495, 7.478, 7.474, and 7.486 ppm for protons H10, H11, H22, H26,

H28, and H35 are observed in the multiplet signals of aromatic

hydrogen (Ar-H), which are located in the quinoxaline group. The

doublet signal detected at δ 8.191 and 8.185 ppm for protons H7

and H30 refer to the existence of (Ar-H), which are located in

the quinoxaline group. The singlet signal found at δ 8.57 ppm for

proton H33 indicates (Ar-H), which is presented in the quinoxa-

line group. Finally, one singlet signal determined at δ 10.195 ppm

for proton H37 shows the appearance of aldehyde proton in the

quinoxaline group in Table S12. The root-mean-square deviation

(RMSD) ppm observed between experimental and calculated val-

ues are very low excepting the H7 atom, the proton ¹H signals at

δ 7.263 to 10.195 ppm. Calculated ¹H NMR chemical shift for the

atoms H9, H10, and H33 shows a superior agreement with the ex-

perimental spectrum.

3.9. (¹³C and ¹H) nuclear magnetic resonance spectral data

NMR spectroscopy is a potent method for structural studies of

chemical compounds [67,68]. The experimental ¹³C and ¹H NMR,

spectra in CDCl₃solvent of the title compound DPQC compound

was shown in Figs. S7 and S8 of the (Supporting Information)

and MDBD compound were depicted in Figs. S9 and S10 of the

(Supporting Information). The theoretical NMR spectra of the ti-

tle compounds are recreated by using DFT/B3LYP method and 6–

311G++(d,p) as basis set.

The slight variation achieved amongst calculated DFT/B3LYP and

experimental spectra values are due to the solvent used. The DPQC

and MDBD title compounds of ¹³C NMR Chemical Shifts, Abso-

lute Shielding tetramethylsilane (TMS) values are 182.4656 and

199.9853 with 31.8221 and 32.5976 (TMS) values for ¹H NMR spec-

tra. As can be observed from Tables S12 and S13 (Supporting In-

formation), the calculated ¹H and ¹³C chemical shift results for

DPQC and MDBD (DFT/B3LYP) values have matched the experimen-

tal data. To generate comparability with experimental observations,

The NMR spectrum of carbon-13 range of chemical shift for

organic molecules is illustrated as generally >100 ppm [71]. The

DPQC title compound indicated a peak chemical shift values at δ

126.77 ppm for (Ar-C) carbon C4 found in the quinoxaline group,

δ 128.41 and 129.81 ppm for (Ar-C) carbon C32 and C34 are in-

dicated with the benzil group. At δ 129.32, 129.41, 129.47, 130.46,

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J.I. Ahamed, G.R. Ramkumaar, P. Kamalarajan et al.

Journal of Molecular Structure 1248 (2022) 131418

Fig. 11. NMR graphical representation of molecule MDBD.

134.76, 137.06, 138.46, 144.22, 154.78, and 155.60 ppm for (Ar-C)

carbon C6, C21, C5, C25, C1, C23, C3, C2, C12, and C13 are found in

the quinoxaline group. Finally, the peak at δ191.36 ppm for (alde-

hyde carbon) C36 was placed in the quinoxaline group shown in

Table S12. The RMSD ppm observed between experimental and cal-

culated values are very low excepting C12 atom, the carbon ¹³C

signals were presented at δ 126.32 to 191.36 ppm. Calculated ¹³C

NMR chemical shift for the atoms C2, C23, and C36 shows a greater

concord with the experimental spectrum.

129.799, 129.051, 131.628, 145.428, 147.068 ppm signals for (Ar-C)

carbon C80, C69, C58, C47, C56, C54, C41, C29, and C20, which are

the presence of triphenylamine. In addition, (¹³C) NMR peaks at δ

128.861, 132.414, 140.114, 140.802, 141.247, 153.528, 154.228 ppm

for (Ar-C) carbon C74, C43, C22, C53, C15, C12, and C11, which

are found to indicating the presence (Ar-C) of 6-methylquinoxalin

group shown in Table S13. The RMSD ppm observed between ex-

perimental and calculated values are very low excepting C34 atom,

the carbon ¹³C signals were presented at δ 126.32 to 191.36 ppm.

Calculated ¹³C NMR chemical shift for the atoms C20, C41, and C74

shows a good deal with the experimental spectrum. The aforemen-

tioned spectrum data is very well aligned by both experimental

and DFT calculation with the structures of the new quinoxaline

DPQC and MDBD derivatives.

The title molecule MDBD proton ¹H NMR spectrum for the

chemical shift values at δ 2.50 ppm for proton H35, shows the

presence of methyl (-CH₃) protons in the quinoxaline group. The

multiplet signals observed at δ 6.936 ppm for proton H8 and δ

6.966 ppm for proton H23, doublet signal observed at δ 7.098 ppm

for proton H72 and δ 7.101 ppm for proton H83, and the other

multiplet signals observed at δ 7.225 ppm for proton H61 and

δ 7.312 ppm for proton H81 which indicates the presence (Ar-

H) of triphenylamines. The doublet of doublet signal was ob-

served at δ 7.584 ppm for proton H77 and δ 7.602 ppm for pro-

ton H46, doublet signal observed at δ 7.907 ppm for proton H26

and δ 7.911 ppm for proton H28, and doublet signal observed at

δ 8.285 ppm for proton H66 and δ 8.301 ppm for proton H44,

indicates the (Ar-H) existence of 6-methylquinoxaline. Finally, the

doublet signal observed at δ 8.033 ppm for proton H68 and δ

8.047 ppm for proton H49 denotes the presence of the (Ar-H)

triphenylamine group shown in Table S13. The RMSD ppm ob-

served between experimental and calculated values are very low

excepting the H23 atom, the proton ¹H signals were presented

at 6.936 to 8.301 ppm. Calculated ¹H NMR chemical shift for the

atoms H28, H61, and H72 shows a greater concord with the exper-

imental spectrum.

3.10. Mass spectrum

The mass spectrum range of synthesized the novel quinoxaline

derivatives with its molecular ion peak observed at m/z 311.40 for

DPQC and m/z 631.73 for MDBD compounds are owing to the ex-

istence of (MH+), which coincides with the molecular mass, their

(m/z) scale ranges observed at 200–2000 presented in Figs. S15 and

S16 (Supporting Information). The observed molecular ion peaks in

the spectra match the predicted molecular structures of the title

compound perfectly. The spectrophotometers were run in positive

scan mode.

3.11. Biological evaluations

3.11.1. Antibacterial activity

The title compounds DPQC and MDBD from formulated pow-

der showed broad-spectrum antibacterial activity against Gram (+)

and Gram (−) bacteria using streptomycin as a positive control. The

DPQC molecule showed potent bactericidal activity with a maxi-

mum of (17.7 1.0 mm) at 2.5 μg/mL against Staphlococcus aureus

A chemical shift peak at δ 21.686 ppm for carbon C34 of the

title molecule MDBD was demonstrated the Methyl (-CH₃) carbon

presented in the quinoxaline group of the carbon-13 NMR spec-

trum. The peaks detected at δ 122.905, 124.879, 126.271, 126.361,

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J.I. Ahamed, G.R. Ramkumaar, P. Kamalarajan et al.

Journal of Molecular Structure 1248 (2022) 131418

Table 2

Antibacterial activity of DPQC against Gram-positive and Gram-negative bacteria.

Organisms

Streptomycin (mm)

Antibacterial activity (mm)

0.5(μg/ml)

1(μg/ml)

1.5(μg/ml)

2(μg/ml)

2.5(μg/ml)

Staphylococcus aureus (MTTC 3615)

Enterococcus faecalis (MTCC 439)

Y. enterocolitica (MTCC 840)

20.1 1.0

19.8 0.5

19.7 0.5

20.1 0.5

12.3 0.5

11.3 0.5

10.3 0.5

12.3 0.5

13.2 0.5

11.9 1.0

11.0 0.5

13.5 0.5

14.4 0.5

12.6 1.0

12.7 0.5

14.5 1.0

15.5 1.1

13.3 0.5

13.6 1.0

15.3 1.0

17.7 1.0

14.8 1.1

15.6 1.0

17.5 1.0

Proteus mirabilis (MTCC 1771)

Table 3

Antibacterial activity of MDBD against Gram-positive and Gram-negative bacteria.

Bacteria

Streptomycin (mm)

Antibacterial activity (mm)

0.5(μg/ml)

1(μg/ml)

1.5(μg/ml)

2(μg/ml)

2.5(μg/ml)

Staphylococcus aureus (MTTC 3615)

Enterococcus faecalis (MTCC 439)

Y. enterocolitica (MTCC 840)

21.6 0.5

21.4 0.5

22.3 0.5

21.0 0.5

15.6 0.5

16.6 0.5

17.1 1.0

15.4 0.5

14.3 0.5

17.3 1.1

17.8 0.5

15.9 1.1

15.3 0.5

17.9 1.0

18.0 1.0

17.7 1.0

17.6 0.5

18.3 0.5

18.8 1.0

18.8 0.5

18.6 1.0

19.0 1.0

19.5 1.0

19.1 1.1

Proteus mirabilis (MTCC 1771)

Fig. 12. Antibacterial activity of DPQC against Gram-positive and Gram-negative

bacteria.

Fig. 13. Antibacterial activity of MDBD against Gram-positive and Gram-negative

bacteria.

(MTCC 3615) and minimum zone of inhibition of (10.3 0.5 mm)

on Y. enterocolitica (MTCC 840) (Table 2 and Fig. 12) at 0.5 μg/mL

respectively. The MDBD molecule showed potent bactericidal ac-

tivity with a maximum of (19.5 1.0 mm) at 2.5 μg/mL against

Y. enterocolitica (MTCC 840) and minimum zone of inhibition of

(14.3 0.5 mm) on Staphylococcus aureus (MTCC 3615) (Table 3 and

Fig. 13) at 1 μg/mL respectively.

leading to increased activity. Because of the presence of the triph-

enylamine group [76–78], the MDBD molecule may be regarded as

an analogue of triphenylamine (a recognised antibacterial).

3.11.2. In vitro antioxidant activity (H₂O₂and dpph radical

scavenging activity)

Yokoyama A. and coworkers examined the antibacterial activi-

ties of 2,3-Bis(bromomethyl)quinoxaline derivatives, and reported

According to a pharmaceutical technique, the H₂O₂scavenging

test was estimated [23]. The ﬁndings of the antioxidant research

(H₂O₂) showed that the produced MDBD synthesized compound

may be a good source of the activity of hydroxyl radical scaveng-

ing.

that

only

2,3-Bis(bromomethyl)-6-ethoxycarbonylquinoxaline

molecule showed activities against Gram-negative bacteria (Es-

cherichia coli, Pseudomonas aerugianosa, and Serratia marcescens)

[72]. As a result, it is possible that it is due to an increase in

the length of the alkyl chain. However, since the DPQC molecule

aldehyde (-CHO) group has no action against Gram (-) bacteria,

the MDBD molecule’s activity against Gram (-) bacteria can be ex-

plained by the source of the offerings of the incorporated aromatic

ring and (–CH₃) groups [73,74], which we know should increase

the lipophilicity of the molecules [75]. This increase in lipophilicity

would improve their permeability through the microbial cell wall,

Hydroxyl radicals (OH˙) are short-lived species possessing a

high aﬃnity for other molecules. OH is a strong oxidizing agent

that can react at a high rate with the majority of lipids, amino

acids, sugars, and metals. Because OH is identiﬁed as the primary

reactive radicals in biological systems, it interacts with nearby

molecules at the point of origin. The substance damages the cell

membrane’s polyunsaturated fatty acid moieties. Hydroxyl radicals

are produced in several ways. OH, scavenging activity of synthe-

12

J.I. Ahamed, G.R. Ramkumaar, P. Kamalarajan et al.

Journal of Molecular Structure 1248 (2022) 131418

Table 4

Table 6

Antioxidant activity of synthesized quinoxaline derivatives.

Anticancer activity of synthesized DPQC and MDBD test compounds measured by

MTT assay and (HepG2) liver cancer cell line.

Sample Name

Control

Test (1 mg/mL)

H₂O₂Scavenging (%)

% of Concentration (μg/ml)

% of cell viability

DPQC

3.8

3.1

18.42

64.21

MDBD

1.36

MDBD

15.75

81.8

78.4

76.6

58.2

45.3

100

89.2

87.1

85.2

83.3

81.2

100

31.25

Table 5

62.5

Antioxidant activity of test compounds 2,3-Diphenylquinoxaline derivatives (DPQC

and MDBD), measured by DPPH assay.

125

250

Concentration (μg/ml)

% of Inhibition

DPQC

Standard Drug

Control (HepG2) cell-line

MDBD

D - Ascorbic acid

100

200

300

400

500

17.99

30.94

40.01

52.32

59.76

19.01

32.31

40.39

54.73

67.48

47.37

55.32

69.43

86.45

90.89

dant process on the DPPH assay. A probe through the literature re-

veals [81,82] that DPPH can be quenched by hydrogen atom trans-

fer (HAT), electron transfer (ET), or a combination of both. In the

compound, MDBD both HAT and electron transfers (ET) mecha-

nisms were involved.

The electron transfer mechanism consists of forming a complex

of an aminium cation radical and DPPH anion. As per the HAT

mechanism, the removal of hydrogen radicals from both MDBD

would reﬂect their antioxidant activities.

3.11.3. In vitro anticancer activity

Most of the quinoxaline derivatives have been observed to be

successful in vitro cytotoxic compounds against a human liver tu-

mour cell line [83,84]. In this study, we analysed all the synthe-

sized new DPQC and MDBD compounds for their anticancer activ-

ity. The (HepG2) liver cancer cell lines-Controls image was repre-

sented in Fig. 16a. amongst the two compounds studied the com-

pound MDBD showed the anticancer activity at the lowest con-

centration of 125 μg/mL (Table 6 and Fig. 16b). This compound

reduced the cell viability to 83.3 % respectively and cell viability

was much more decreased to 81.2 % respectively at 250 μg/mL.

The HepG2 - liver cancer cells were tested at concentrations from

15.75 μg/mL to 250 μg/mL. The compound DPQC showed potent

anticancer activity only at a higher concentration of 250 μg/mL.

The resultant (HepG2) cell line image and graphical representa-

tions of DPQC were shown in Fig. 16c. The anticancer activities of

synthesized DPQC and MDBD test compounds measured by MTT

assay and (HepG2) liver cancer cell line images were given in

Fig. 1 7.

Fig. 14. In vitro DPPH radical scavenging activity of test compounds DPQC and

MDBD.

sized compounds determined that MDBD possessed the greatest

antioxidant capacity compared to DPQC. In vitro, antioxidant ac-

tivities were demonstrated in Table 4.

The synthesized compounds (DPQC and MDBD) were evaluated

for their capability to scavenge the free radicals formation which

was measured by the DPPH assay method [79,80]. The antioxidant

activities of the synthesized compound were shown in Table 5. The

D-ascorbic acid (Vitamin C) was utilized as a standard antioxidant.

The IC₅₀values for each compound were calculated and found

that all the antioxidant tested compounds 2,3-Diphenylquinoxaline

derivatives such as DPQC and MDBD possess IC₅₀values in close

ranges from 365.4303–382.2765 μg/mL. There was not much dif-

ference between these compounds in scavenging the free radical

results Fig. S17 (Supporting Information). When compared to the

standards, all the compounds exhibited activity of free radical scav-

enging, particularly the compound MDBD showed strong antioxi-

dant activity (67.48 %) at the concentration of 500 μg/mL followed

by compound DPQC showed (59.76 %) and D-ascorbic acid (Vitamin

C) showed the activity of 90.89 % of free radical scavenging con-

centration at 500 μg/mL (Table 5). All the compounds possessed

good radical scavenging activity (Fig. 14).

3.12. In silico section

3.12.1. Molecular docking studies

The compounds studied, DPQC and MDBD showed signiﬁcant

in vitro anticancer activity. Hence, these compounds were further

investigated in silico molecular docking analysis against 3F66 (c-

Met-kinase; a hepatocyte growth factor) protein target. Receptor

tyrosine kinases (RTKs) are interesting pharmacological targets im-

portant for developing tumours and controlling the many routes

of signal transduction inside the cell. The molecular proﬁle of pa-

tients, particularly based on the molecular pathways associated

with cancer start and development, is created according to new

treatments. The c-metal acts on hepatocyte growth factor (HGF)

and the reshaping, migration, morphogenesis, cell development,

differentiation, and angiogenesis of the epithelial tissue [85–87].

Deregulated activation of the c-Met-signalling pathway through

multiple mechanisms like activation, mutation, gene ampliﬁcation,

and heterodimerization has been reported to correlate with high

tumour grade and the lower rate of survival in most cancers [88].

Moreover, in 2011, c-Met-was found as a marker of pancreatic can-

cer stem cells, which made it a suitable therapeutic target for can-

cer treatment [89]. Applying the scoring functions to the AutoDock

The plausible mechanism for the antioxidant activity of MDBD

against DPPH is exhibited in Fig. 15. Of all the synthesized com-

pounds DPQC and MDBD, the compound MDBD exhibited excel-

lent, explicit from Fig. 15. According to the mechanism, we have

proved that the triphenylamine group participates in the antioxi-

˚

Vina software [90]. The 3F66 resolution was 1.4 A [31] for x-ray

13

J.I. Ahamed, G.R. Ramkumaar, P. Kamalarajan et al.

Journal of Molecular Structure 1248 (2022) 131418

Fig. 15. Plausible antioxidant mechanism of compound MDBD against DPPH radical.

Fig. 16. (a) (HepG2) liver cancer cell lines-Controls. (b) (HepG2) liver cancer cell lines image MDBD. (c) (HepG2) liver cancer cell lines image DPQC.

Fig. 17. Anticancer activities of synthesized DPQC and MDBD test compounds measured by MTT assay and (HepG2) liver cancer cell line.

diffraction. The Root Mean Square Deviation (RMSD) should be ap-

(rmsdl.b and rmsdu.b). Furthermore, the inhibition constants

for all compounds were computed and recorded using Ki=exp

(ꢀG/RT), where = ꢀG, R and Tare docking energy, gas constant

(1.9872036 × 10⁻³kcal/mol), and room temperatures (298.15 K),

were computed and recorded. Let’s examine each docking method

˚

prox. 2 A for a molecular docking process, which value is recog-

nized to be trustworthy for docking [91].

The Human c-Met-Kinase receptor has been presented with

the binding aﬃnity energy values and RMSD values as per

14

J.I. Ahamed, G.R. Ramkumaar, P. Kamalarajan et al.

Journal of Molecular Structure 1248 (2022) 131418

Table 7

The ligand- receptor residue interaction between DPQC, MDBD, and Standard drug Trivatinib with 3F66 protein.

˚

S.NO

Pub chem. Id

3F66

Ligand Name

DPQC

Residue Interaction

Type of bond

Distance (A)

1

A: ASN1175: NH-:UNK0:O24

A: ASP1180: OD2-:UNK0

A: PHE1216-:UNK0

Hydrogen

2.09

3.74

3.92

3.87

4.03

2.91

5.68

5.08

5.68

5.14

4.39

5.13

2.2

π-Anion Electrostatic

π- π- Stacked Hydrophobic

Hydrogen

A: PHE1216-:UNK0

A: ARG1086:NH -:UNK0:N6

A: MET1211: SD-:UNK0

: UNK0-A: VAL1092

2

3

3F66

MDBD

π-Sulfur

π-Alkyl Hydrophobic

Hydrogen

: UNK0-A: ALA1226

: UNK0-A: ALA1108

: UNK0-A: MET1211

Standard Drug

A: LYS1248:H -:UNK0:O1

A: ASN1288:C -:UNK0:O1

: UNK0:H-A: SER1236:OG

A: LYS1248: NZ-:UNK0

A: LYS1248-:UNK0

Trivatinib (Pbchem ID

– 11,494,412)

Hydrogen

3.53

2.91

4.12

3.35

4.8

Hydrogen

π-Cation Electrostatic

Alkyl Hydrophobic

A: PRO1283-:UNK0

5.47

Fig. 18. The molecular docking results of the title compound (DPQC) (a) Hydrogen bond Interaction of DPQC ligand with 3F66 protein (b) Hydrogen bond Receptor-side

surface Interaction of DPQC ligand with 3F66 protein. (c) 2D-Hydrogen bond Interaction representation of DPQC ligand with 3F66 protein.

for the proteins utilized one by one. The Inhibition constant (ki)

describes the interaction between the ligand and an enzyme sub-

stance, whereas, ki measures the ligand-binding aﬃnity to the pro-

tein. If (ki) is lower, less medication is essential to inhibit the en-

zyme’s activity. Additionally, the (ki) value is found to be con-

ﬁrmed if a medication is going to block an enzyme and conse-

quence in a clinically relevant speciﬁc drug with a substrate for

the enzyme [92–94]. The binding aﬃnity and inhibition constant of

(ki) of all resulting ligands are presented in Table S14 (Supporting

Information). The results indicate, with residual interactions, types

of bond, and bond lengths, that all DPQC, MDBD, and Standard

Drug Tivantinib ligands could strongly occupy the active site of

3F66 was shown in Table 7 In this study, we have depicted in-

termolecular interactions of different DPQC, MDBD, and Tivantinib

ligands with the Human c-Met-Kinase (PDB code: 3F66) protein,

respectively.

colour), π-anion electrostatic interactions are shown (Dark Pink

colour), and ﬁnally, π-π stacked hydrophobic interactions have

been shown (yellow colour).

The ligand MDBD (within 3F66) molecular docking ligand-

receptor hydrogen bond interactions, Receptor side hydrogen bond

interactions, and their 2D-ligand-receptor hydrogen bond inter-

action graphical representation were given in (Fig. 19a, b, and

c) with a binding energy value of -10.8 (kcal/mol), 0.01187 μM

inhibition constant (ki) and also presented one hydrogen bond

interaction between (ARG1086:NH amino acid residue and N6

˚

atom; bond angle of 2.91 A), respectively; two π-Sulfur inter-

actions were formed between the triphenylamine group with

(Two MET1211: SD amino acid residues; bond angle values are

˚

5.08 and 5.68 A), respectively; four π-Alkyl Hydrophobic interac-

tions were formed between the triphenylamine group with (Four

VAL1092/ALA1226/ALA168/MET1211 amino acid residues; bond an-

˚

The ligand DPQC (within 3F66) molecular docking ligand-

receptor hydrogen bond interactions, Receptor side hydrogen bond

interactions, and their 2D-ligand-receptor hydrogen bond interac-

tion graphical representation were given in (Fig. 18a, b, and c)

with a binding energy value of -7.9 (kcal/mol), 1.59526 μM inhi-

bition constant (ki) and also presented one hydrogen bond inter-

action between (ASN1175: NH amino acid residue and O24 atom;

gle values are 5.68, 5.14, 4.39, and 5.13 A). Fig. 19a shows clearly

that the hydrogen bond is denoted (green colour), π-Sulfur inter-

actions are shown (yellow colour), and ﬁnally, π- Alkyl hydropho-

bic interactions have been shown (pink colour).

In our study, Tivantinib [95] ligand was selected as a standard

drug because, generally, Tivantinib is an orally bioavailable small

molecule inhibitor of c-Met-with potential antineoplastic activity.

The c-Met-inhibitor ARQ 197 binds to the c-Met-protein and dis-

rupts c-Met-signal transduction pathways, inducing cell death in

tumour cells over expressing c-Met-protein or expressing the con-

stitutively activated c-Met-protein. The ligand Tivantinib (within

3F66) molecular docking ligand-receptor hydrogen bond interac-

tions, Receptor side hydrogen bond interactions, and their 2D-

ligand-receptor hydrogen bond interaction graphical representation

˚

bond angle of 2.09 A), respectively; two π-anion electrostatic in-

teractions were formed between the quinoxaline group with (Two

ASP1180: OD2 amino acid residues; bond angle values are 3.74 and

˚

3.92 A), respectively; two π- π stacked hydrophobic interactions

were formed between the quinoxaline group with (Two PHE1216

˚

amino acid residues; bond angle values are 3.87 and 4.03 A).

Fig. 18a shows clearly that the hydrogen bond is denoted (Green

15

J.I. Ahamed, G.R. Ramkumaar, P. Kamalarajan et al.

Journal of Molecular Structure 1248 (2022) 131418

Fig. 19. The molecular docking results of the title compound (MDBD) (a) Hydrogen bond Interaction of MDBD ligand with 3F66 protein (b) Hydrogen bond Receptor-side

surface Interaction of MDBD ligand with 3F66 protein. (c) 2D-Hydrogen bond Interaction representation of MDBD ligand with 3F66 protein.

Fig. 20. The molecular docking results of the title compound (Standard Drug Trivatinib) (a) Hydrogen bond Interaction of Trivatinib ligand with 3F66 protein (b) Hydrogen

bond Receptor-side surface Interaction of Trivatinib ligand with 3F66 protein. (c) 2D-Hydrogen bond Interaction representation of Trivatinib ligand with 3F66 protein.

were given in (Figs. 20a, b, and c) with a binding energy value of

-8.3 (kcal/mol), 0.81153 μM inhibition constant (ki) and also pre-

sented two hydrogen bond interactions between carbonyl (C=O)

functional groups which were presented in the pyrrolidine ring

with (LYS1248:H amino acid residue and O1 atom; bond angle of

been synthesized by direct condensation reaction, and their vari-

ous physical and spectroscopic techniques, particularly, FT-IR, UV-

Visible spectroscopy, ¹H, and ¹³C NMR, ESI-Mass spectrum, and el-

emental (CHNS/O) analysis have been carried out. The structural

geometrical parameters, vibrational, electronic, HOMO-LUMO, Mul-

liken population analysis, and Molecular electrostatic potentials

(MEPs) were carried out by the DFT calculations on the B3LYP/6–

311G++(d,p) basis set. An excellent agreement between experi-

mental and calculated wavenumbers and all observed wavenum-

bers have been assigned. The Frontier Molecular Orbitals (FMOs)

analysis of (HOMO-LUMO) energy (Gap (eV) = 3.8448) for the

DPQC molecule and (Gap (eV) = 3.1212) for the MDBD molecule. In

DFT, the electron aﬃnity (A) study of DPQC and MDBD showed a

low electron aﬃnity HOMO-LUMO value of 2.4165 (eV) and 1.7226

(eV). The NLO investigations conﬁrm that the DPQC and MDBD

compounds are excellent NLO materials. Furthermore, in the bi-

ological evaluations studies, the antibacterial activities have been

done for the novel DPQC and MDBD compounds against Gram

(+) and Gram (−) bacteria using the disc diffusion technique and

the result discovered that the MDBD compound showed impor-

tant antibacterial activity against Gram (+) and Gram (−) bacte-

ria owing to the existence of triphenylamine group. The compound

MDBD showed a strong hydrogen peroxide (H₂O₂) and DPPH radi-

cal scavenging antioxidant activities and revealed potent anticancer

activity against human liver cancer (HepG2) cell lines. In molec-

ular docking investigation MDBD ligand, which has shown the

best binding energy value of -10.8 (kcal/mol), and a 0.01187 μM

inhibition constant (ki) against the Human c-Met-Kinase (PDB

code: 3F66; chosen active site A) involved amino acids such as

A: ARG1086, A: MET1211, A: VAL1092, A: ALA1226, A: ALA1108,

A: MET1211. Hence, it has given superior binding energy and very

powerful inhibition constant (ki) values compared to both DPQC

and trivatinib ligands. Hence, the MDBD ligand will be a medica-

tion needed to inhibit the Human c-Met-Kinase (PDB code: 3F66)

protein. The synthesized quinoxaline derivatives thus have certain

biochemical potential and might be more likely to create medicines

associated with diverse microbial, fungal and viral illnesses.

˚

2.20 A), (ASN1288:C amino acid residue and O1 atom; bond angle

˚

of 3.53 A), and one hydrogen bond interaction between the indole

group with (SER1236:OG amino acid residue and H atom; bond an-

˚

gle of 2.91 A), respectively; two π-Cation Electrostatic interactions

were formed between the 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline

group with (Two LYS1248: NZ amino acid residues; bond angle val-

˚

ues are 4.12 and 3.35 A), respectively; two alkyl hydrophobic in-

teractions were formed between the 5,6-dihydro-4H-pyrrolo[3,2,1-

ij]quinoline group with (Two LYS1248 amino acid residues; bond

˚

angle values are 4.80, and 5.47 A). Fig. 20a shows clearly that

the hydrogen bond is denoted (Green colour), π-Cation Electro-

static interactions have been shown (pink colour), and ﬁnally, alkyl

hydrophobic interactions have been shown (pink colour). In this

molecular docking study, the newly synthesized DPQC ligand has

shown the best binding energy, as well as good inhibition con-

stant (ki) values, with these values being very close to the standard

drug, tivantinib. Human c-Met-Kinase in complex with quinoxaline

inhibitor (PDB code: 3F66; chosen active site A) protein with the

target compound MDBD, which has shown a signiﬁcant binding

interaction energy value of-10.8 (kcal/mo) compared to the known

standard drug tivantinib-8.3 (kcal/mol). The binding interaction en-

ergy value of DPQC was -7.9 (kcal/mol), which was nearly equal to

tivantinib.

➢ The Residue Interaction column (UNK0) Symbol is described as

ligand side with its functional groups such as O, S, N…..ect.

➢ A: is indicates as a protein chain.

4. Conclusions

The present work describes a series of novel DPQC and MDBD

possessing quinoxaline moiety containing compounds that have

16

J.I. Ahamed, G.R. Ramkumaar, P. Kamalarajan et al.

Journal of Molecular Structure 1248 (2022) 131418

Credit author statement

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The authors are delighted to thank C. Kandaswami Naidu Col-

lege for Men, Department of chemistry (SHIFT – II) and LIFE (Loy-

ola Institute of Frontier Energy) for supporting this study by pro-

viding us with laboratory facilities, instrumental facilities and in-

frastructural facilities. Also, thanks to the Plant Biology & Biotech-

nology Department, Loyola College (Autonomous), for providing

the laboratory facilities for in vitro studies and to the Department

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Novel quinoxaline derivatives of 2, 3-diphenylquinoxaline-6-carbaldehyde and 4, 4′-(6-methylquinoxaline-2,3-diyl)bis(N,N-diphenylaniline): Synthesis, structural, DFT-computational, molecular docking, antibacterial, antioxidant, and anticancer studies

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