Synthesis, characterization, biological screening and molecular docking of Zn(II) and Cu(II) complexes of 3,5-dichlorosalicylaldehyde-N4-cyclohexylthiosemicarbazone

Article abstract of DOI:10.1002/aoc.5294

A 3,5-dichlorosalicylaldehyde-N⁴-cyclohexylthiosemicarbazone (C₁₄H₁₆Cl₂N₃OS) and its complexes [Zn(dsct)(phen)]·DMF (1), [Zn(dsct)(bipy)]·DMF (2), [Cu(dsct)(bipy)]·DMF (3) (phen?=?1,10-phenathroline,

Full text of DOI:10.1002/aoc.5294

Received: 22 February 2019
DOI: 10.1002/aoc.5294
Revised: 1 May 2019
Accepted: 1 October 2019
F U L L P A P E R
Synthesis, characterization, biological screening and
molecular docking of Zn(II) and Cu(II) complexes of 3,5‐
dichlorosalicylaldehyde‐N4‐cyclohexylthiosemicarbazone
Nimya Ann Mathews1 | P.M. Sabura Begum1 | M.R. Prathapachandra Kurup1,2
1 Department of Applied Chemistry,
Cochin University of Science and
A 3,5‐dichlorosalicylaldehyde‐N4‐cyclohexylthiosemicarbazone (C14H16Cl2N3OS)
Technology, Kochi 682 022Kerala, India
2 Department of Chemistry, School of
and its complexes [Zn(dsct)(phen)]·DMF (1), [Zn(dsct)(bipy)]·DMF (2), [Cu(dsct)
(bipy)]·DMF (3) (phen = 1,10‐phenathroline, bipy = 2,2’bipyridine) were synthe-
Physical Sciences, Central University of
Kerala, Tejaswini Hills, Periye, Kasaragod
sized and characterized by CHN analysis, FT‐IR, UV–vis and NMR spectra. The
671 320, India
molecular structure of the thiosemicarbazone (H2dsct) and its complexes have
been resolved using single crystal XRD studies. In the complexes,
thiosemicarbazone exist in the thioiminolate form and acts as dideprotonated
tridentate ligand coordinating through phenolic oxygen, thioiminolate sulfur
and azomethine nitrogen. The antibacterial activity of the prepared compounds
were screened against Escherichia coli, Salmonella typhi, Enterobacter aerogenes,
Shigella dysentriae, Bacillus cereus, Staphylococcus aureus. All the complexes
showed activity against bacterial strains E.coli and Salmonella typhi. The
thiosemicarbazone showed activity against three bacterial strains such as E. coli,
Enterobacter aerogenes and Shigella dysentriae. Complex 2 showed very good anti-
bacterial activity as compared to standard drug (Ampicillin) against the bacterial
strain, Salmonella typhi. Finally, the thiosemicarbazone and its complexes have
been used to accomplish molecular docking studies against an Epidermal Growth
Factor Receptor (EGFR) and breast cancer mutant 3hb5‐oxidoreductase to deter-
mine the most preferred mode of interaction. The results confirm that the complex
[Cu (dsct)(bipy)]·DMF(3) showed the highest docking score as compared to other
complexes under study. The [Cu(dsct)(bipy)]·DMF(3) complex was evaluated for
their anticancer activities against breast cancer cell line (MCF‐7) and normal
L929 (Mouse Fibroblast) cell line. It was found that the compound showed an
LC50 of 6.25 μg/mL against breast cancer cell line (MCF‐7).
Correspondence
M. R. Prathapachandra Kurup,
Department of Chemistry, School of
Physical Sciences, Central University of
Kerala, Tejaswini Hills, Periye. Kasaragod,
671 320, India.
Email: mrpcusat@gmail.com
Funding information
University Grants Commission, Grant/
Award Number: Nov 2017‐111132
KEYWORDS
antibacterial activity, crystal structures, molecular docking, MTT, Thiosemicarbazones
1 | INTRODUCTION
preparation, excellent complexation, variety of coordina-
tion modes and useful pharmacological properties and
Thiosemicarbazones are a class of Schiff base compound of
chelating bio ligands that contain a thiourea moiety and
they attract considerable attention due to their ease of
pharmacological applications.[1,2] They are versatile
ligands and efficient metal chelators. A number of
reasons have been responsible for the versatility in their
Appl Organometal Chem. 2019;e5294.
wileyonlinelibrary.com/journal/aoc
© 2019 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.5294

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MATHEWS ET AL.
coordination, such as, intramolecular hydrogen bonding,
bulkier coligands, steric crowding on the azomethine
carbon atom and π‐π stacking interaction. They act as
chelating ligand with certain metal ions, by bonding with
the sulfur and hydrazine nitrogen atoms. They are also
versatile ligands which can coordinate in both their neutral
[3] and anionic forms.[4] They are a privileged ligands with
their ability to create complexes with wide range of transi-
tion metal ions yielding stable and strongly coloured metal
complexes.[5] Different variety of thiosemicarbazone deriv-
atives have been synthesized as antibacterial, antiviral,
antifungal, antioxidant, anti‐inflammatory and antiprolif-
erative agents.[6–9] It is found that Cu (II) complexes with
heterocyclic ligand show biological activity.[10] The nitro-
gen and sulfur donor atoms present in the
thiosemicarbazone might be the reason for its potential
biological activity.[11] Recently Ayman et al. reported anti-
bacterial studies of newly synthesized cobalt (II, III), nickel
this treatment. Hence there is an emerging need to iden-
tify new drugs that are effective and safe for the treatment
of cancers. The copper and zinc complexes of
thiosemicarbazones are a class of compounds with medic-
inal property had reported earlier in 1960s. Very lately, a
copper complex [CuII (pyrimol)Cl] have been reported by
Reedijk and co‐ workers which is cytotoxic towards L1210
murine leukaemia and A2780 human ovarian carcinoma
cell line.[20] Palaniandavar, Chakravarty, Von and their
co‐workers reported the function of hydrophobicity of
ligands in many ternary copper(II) complexes, which
results in DNA binding and cleavage and induce apopto-
[21]
sis in various cancer cell lines.
Bearing in mind that
ONS donor system is a common feature for all the com-
pounds with carcinostatic potency, we have carried out
molecular docking on the synthesized compounds with
receptor of breast cancer (3hb5) and EGFR TK (1 m17)
and also the cytotoxic studies of the complex using MTT
assay.
(II) and copper (II) complexes with salicylaldehyde N4‐
[9b]
antipyrinylthiosemicarbazone
. 3‐Aminopyridine‐2‐
carboxaldehyde thiosemicarbazone (triapine) has been
the most studied thiosemicarbazone which has entered
phase II clinical trials as a chemotherapeutic agent.[12,13]
But it ended up with side effects.
2 | EXPERIMENTAL SECTION
2.1 | Materials
Molybdenum complexes of salicylaldehyde thiosemi-
carbazones show in vitro DNA binding along with
antitumour activity.[14] Biological activities of complexes
like DNA binding, antibacterial and cytotoxic activities of
Ni(II) complexes of substituted salicylaldehyde thiose-
micarbazones were well explored.[15,16] Kalairasi et al.
reported a Ni (II) compex of an ONS donor thiose-
micarbazones as an antiproliferate towards MCF‐7 and
HeLa cell lines.[17]
In this paper, our attention is directed to the design of
Zn(II) and Cu(II) complexes of a thiosemicarbazone with
heterocyclic bases as secondary ligands. Structures of
many biomolecules contain copper and zinc ions, which
are essential for their function.[18] The design of the pro
ligand is important for synthesis of more effective drugs
with less side effects. Copper complexation with
thiosemicarbazone was an effective anticancer strategy.
Studies have revealed that the introduction of planar aro-
matic N‐containing ligands such as bipyridine and its
derivatives that are similar to the purine and pyrimidine
bases can produce complexes with promising properties
for the design and development of drugs due to their
potential to interact with DNA and proteins.[19]
Cyclohexylisothiocyanate (Alfa Aesar), hydrazine hydrate
(Sigma Aldrich), 3,5 dichlorosalicylaldehyde, zinc acetate,
copper acetate were of Analar grade and purchased from
commercial
sources.
The
solvents
methanol
(Spectrochem), acetonitrile (Spectrochem) and DMF
(Spectrochem) were used without further purification.
2.2 | Synthesis of 3,5‐
dichlorosalicylaldehyde‐N4‐cyclohexyl
thiosemicarbazone
The preparation of this compound involves a two‐step
process (shown in Schemes 1 and 2):
• Step 1.
Preparation of N4‐cyclohexylthiosemicarbazide.
In the first step, cyclohexylisothiocyanate (2 ml,
15 mmol) in 20 ml methanol and hydrazine hydrate
(4.3 ml, 90 mmol) in 20 ml methanol were mixed and
the resulting solution was stirred. The resulting colourless
product was filtered, washed with methanol and dried in
vacuo.
Nowadays, cancer is undoubtedly the most alarming
threat faced by humanity and one of the primary targets
relating to the medicinal chemistry. The most frequently
used treatments for breast cancer and other cancers till
date is chemotherapy. But along with the affected cells,
normal proliferating cells are also getting destroyed by
• Step 2.
Synthesis of 3,5‐dichlorosalicylaldehyde‐N4‐cyclohexy-
lthiosemicarbazone (H2dsct).

MATHEWS ET AL.
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SCHEME 1 Synthesis of
cyclohexylthiosemicarbazide
SCHEME 2 Synthesis of 3,5‐dichlorosalicylaldehyde‐N4‐cyclohexylthiosemicarbazone
2.3.3 | [Cu (dsct)(bipy)]·DMF (3)
In the second step, 20 ml of acetonitrilic solution (15 ml)
of N(4)‐cyclohexylthiosemicarbazide (0.173 g, 1 mmol) was
added to a solution of 3,5‐dichlorosalicylaldehyde (0.191 g,
1 mmol) in 20 ml acetonitrile and the reaction mixture was
refluxed for 1 hr after adding a drop of glacial acetic acid.
The product was filtered, washed with acetonitrile and
dried in vacuo. Yield: 0.1408 g (80%).1H‐NMR (dmso, ∂
ppm); 11.5 (1H,s), 8.3 (1H,s), 8.2 (1H,d), 7.9 (1H,s), 7.6
(1H,d), 4.2 (1H,t), 1.1–1.9 (1H,d); M.P.: 129 °C (Figure S1).
The thiosemicarbazone, H2dsct (1 mmol, 0.346 g) was dis-
solved in methanol‐DMF mixture and2,2′‐bipyridine
(1 mmol, 0.156 g) in methanol was added to it. It was then
followed by the addition of copper acetate (1 mmol,
0.199 g). The resulting solution was further refluxed for
about 4 hrs and was then allowed to cool. Dark green
crystals were formed over a period of 7 days, which was
then washed with methanol and finally dried in vacuo.
Yield: 0.248 g (78%)
2.3 | Synthesis of metal complexes
2.3.1 | [Zn(dsct)(phen)]·DMF (1)
2.4 | Physical measurements
Elemental (CHN) analysis were carried out using a Vario
EL III CHNS analyser. Infrared spectra were recorded on
a JASCO FT‐IR‐5300 Spectrometer in the 4000–400 cm−1
range using KBr pellets. Electronic spectra were recorded
on Thermo Scientific Evolution 220 model UV–visible
spectrophotometer in the 200–1000 nm range using solu-
tions in DMF. Molar conductivities of the complexes in
DMF solutions (10−3 M) at room temperature were mea-
sured using a Systronic model 303 direct reading conduc-
A methanolic solution of 1,10‐phenanthroline (1 mmol,
0.198 g) was added to a hot solution of the H2dsct
(1 mmol, 0.340 g) with constant stirring which was
followed by the addition of the zinc acetate (1 mmol,
0.219 g) in the solid form. The above dark green solution
was refluxed for about 4 hrs and allowed to cool. It was
kept aside for 1 week. Yellow colored crystals were
formed on recrystallization from DMF. It was filtered,
washed with methanol and dried in vacuo. Yield:
0.469 g (75%).
1
tivity meter. H NMR spectra of the thiosemicarbazone
and its Zn (II) complexes were recorded using Bruker
AMX 400 FT‐NMR Spectrometer with DMSO‐d6 as the
solvent and TMS as internal standard.
2.5 | X‐ray crystallography
2.3.2 | [Zn(dsct)(bipy)]·DMF (2)
The complex [Zn(dsct)bipy]·DMF was prepared by
refluxing a hot solution of H2dsct and 2,2′‐bipyridine
(1 mmol, 0.156 g) in methanol‐DMF mixture with
methanolic solution of zinc acetate (1 mmol, 0.219 g) for
4 hrs. It was kept aside for slow evaporation for 1 week.
The microcrystals obtained were separated and filtered.
They were washed with methanol and finally dried in
vacuo. Yield: 0.230 g (72%)
Single crystal of thiosemicarbazone and its complexes with
suitable dimensions were selected and mounted on a
Bruker SMART APEXII CCD diffractometer, equipped
with a graphite crystal, incident‐beam monochromator
and a fine focus sealed tube with Mo Kα (λ = 0.71073 Å)
radiation as the X‐ray source. The unit cell dimensions
were measured and the data collection was performed at
292(2) K. The programs APEX2 and SAINT were used for

4 of 14
MATHEWS ET AL.
cell refinement and SAINT and XPREP were used for data
reduction.[22] Absorption corrections were carried out
using SADABS based on Laue symmetry using equivalent
reflections.[23] The structures were solved by direct
methods and refined by full‐matrix least‐squares refine-
2.7 | Molecular docking studies
Cancer is the uncontrolled growth of abnormal cells. The
epidermal growth factor (EGFR) is highly expressed in
different types of cancers like colon, breast, and bladder
cancers.[29] Targeting this receptor is a good policy for
the design of new anticancer drugs.[30] Among the various
cancers, breast cancer is one of the most recurring world-
wide and deadliest cancers that have high number of
mortality rates among females.
The key tool in computational drug design is molecular
docking.[31] The focus is to simulate the molecular recogni-
tion process. It aims to attain an optimized conformation
for the drug and the protein with a relative orientation
resulting in minimized overall free energy. In this paper,
we used molecular docking of thiosemicarbazone (H2dsct)
and the two complexes with the ATP binding site of EGFR‐
TKs (1 m17)[32] and breast cancer (3hb5)[33] by Auto‐Dock.
Crystal Structure of PDB ID: 1 m17 and 3hb5 were obtained
from protein data bank (http://www.rcsb.org). All bound
water molecules were eliminated and the polar hydrogens
were added. The ligand molecules in the cif format is con-
verted to pdb format using mercury software.
[24]
ment on F2 using SHELXL‐97 and SHELXL‐ 2018/3
provided in WinGX [25]. The molecular and crystal
structures were plotted using DIAMOND version 3.2 g [26]
and ORTEP.
In the H2dsct and metal complexes, anisotropic refine-
ment were performed for all non‐hydrogen atoms and all
H atoms on C were placed in calculated positions, guided
by difference maps, with C–H bond distances 0.93–0.96 Å.
H atoms were assigned as Uiso = 1.2Ueq (1.5 for Me). In
complexes 1 and 2, the N3–H3’ and N8–H8’ H atoms were
located from a difference map and their distances were
restrained to 0. 88 □ 0.01 Å.
In [Zn(dsct)(phen)]·DMF (1), the reflections (0 1 1),
(0 1 0) and (3 3 7) were omitted due to bad agreement.
In [Zn(dsct)(bipy)]·DMF (2), some of the reflections are
omitted due to bad agreement. In [Cu (dsct)(bipy)]·DMF
(3), the DMF molecule is disordered overs two sites with
0.755(7) for the major and 0.245(7) for the minor occu-
pied sites. The geometry of the minor disordered part
was restrained to be planar by FLAT instruction. SIMU
command has been given to restrain the atoms in the
DMF molecule to be similar. The bond distances of
the minor disordered DMF part was constrained to be
similar to that of the major disordered part by SAME
instruction. Some reflections in this complex was also
omitted owing to bad agreement.
2.8 | MTT assay
An in vitro cytotoxicity of the selected compound was tested
by MTT assay method. Cells were placed in a 96 well tissue
culture plate for 24 hrs incubation before adding complex,
so as to allow attachment of cell to the wall of the plate.
Non treated control cells were also maintained. After
24 hrs of incubation period, the sample content in wells
were removed and 30 μl of reconstituted MTT solution was
added to all test and cell control wells. The plate was gently
shaken well and incubated at 37 °C in a humidified 5% CO2
incubator for 4 hrs. After the incubation period, the super-
natant was removed and 100 μl of MTT Solubilization Solu-
tion (DMSO) was added and the wells were mixed gently by
pipetting up and down in order to solubilize the formazan
crystals. The absorbance values were measured by using
microplate reader at a wavelength of 540 nm.
2.6 | Antibacterial activity
Antibacterial activities were screened in vitro against the
following organisms, E. coli, Salmonella typhi, Entero-
bacter aerogenes, Shigella dysentriae, Bacillus cereus and
Staphylococcus aureus. The solutions of ampicillin
(antibacterial drug) was used as standard drug. The disc
agar diffusion method[27] was employed for the determi-
nation of antimicrobial activities. 1 mg/ml of each com-
plex is taken for the study. The compounds under
investigation were dissolved in DMSO to a final concen-
tration of 100 mg/ml.The antibacterial activity was
compared with that of positive control of commercial
and the most available drug, ampicillin. All the tests
were performed in duplicate. The complex has good
antimicrobial activity, if the inhibition zone measures
~2–3 mm and more effective if the inhibition zone is
greater than 3 mm. If there is no inhibition zone, then
the complex has no activity on the bacterium.[28]
The percentage of growth inhibition was calculated
using the formula:
Mean OD Samples x 100
%of viability
¼
Mean OD of control group
3 | RESULTS AND DISCUSSION
A newly synthesized thiosemicarbazone and its three com-
plexes were synthesized and characterized by elemental

MATHEWS ET AL.
5 of 14
analysis, molar conductivity measurements, IR, electronic
and 1H NMR spectral studies. The complexes were synthe-
sized by refluxing an equimolar mixture of appropriate
thiosemicarbazone with zinc/copper acetate along with
the corresponding heterocyclic bases. Complexes 1 and 2
are yellow in colour whereas complex 3 is dark green in col-
our. In all the complexes, thiosemicarbazone exists in the
thioiminolate form and act as a dideprotonated tridentate
may be due to benzene ring, imine and thiocarbonyl
groups present in the compound. These intraligand bands
have undergone marginal changes during complexation.
The spectra of these bands in complexes are found to be
shifted in the region of 325–340 nm (29,425 ɛ/
M−1 cm−1). In Zn complexes, the π → π* bands are
shifted to longer wavelength region as a result of the C–
S bond being weakening and conjugation system enhanc-
ing on complexation.[38] In addition to this, a new band in
the range 390–410 nm (17,340 ɛ/M−1 cm−1) is observed
for complexes which can be assigned to the Ophenolate-
Zn, Nazomethine → Zn and S → Zn LMCT transitions.[39,40]
But in [Cu(dsct)(bipy)]·DMF (3) absorptions in visible
region in the 560–570 nm (214 ɛ/M−1 cm−1) range are
attributable to d‐d transitions, as observed in many cop-
per(II) complexes. In the Cu (II) complex, an intense
band observed at 420 nm (17304 ɛ/M−1 cm−1) is assigned
to ligand to metal charge transfer transition. The Cu(II)
complexes with a square pyramidal geometry usually
exhibits three spin allowed transitions; A1g ← B1g,
ligand
coordinating
through
phenolic
oxygen,
thioiminolate sulfur and azomethine nitrogen. The metal
complexes prepared are stable towards air and moisture
at room temperature. They are insoluble in water but solu-
ble in dipolar aprotic solvents like DMF and DMSO. On the
basis of elemental analysis data, stoichiometry was
assigned to the thiosemicarbazone and metal complexes,
which was further confirmed by single crystal X‐ray dif-
fraction studies (Table S1). The molar conductivity mea-
surements were measured in DMF (10−3 M) at room
temperature for the H2dsct and its metal complexes. The
values were in the range 2–10 Ω−1 cm2 mol−1 suggesting
that the complexes are non‐electrolytic in nature and
B
2g ← B1g and Eg ← B1g, but due to the very small energy
remain un‐dissociated in DMF [34]
.
difference between the d levels, the bands usually
appeared are weak and overlapped, they become difficult
to resolve them into separate components.[40]
3.1 | IR spectra
The characteristic IR bands of the complexes have shown
significant changes as compared to that of the parent
thiosemicarbazone and the shift of some of the character-
istic vibrational frequency of the ligand upon complexa-
tion provides the mode of binding around the metal ion.
The important IR frequencies of ligand and its complexes
along with their relative assignments are given in Table
S2. The infrared spectral data of the thiosemicarbazone
derivative and complexes 1–3 are presented in the above
table with their tentative assignments. The new band
found at ν = 1596 cm−1 is due to C=N bond resulting
from enolization of the thiosemicarbazone ligand and
the one at ν = 1509 cm−1 is due to newly formed C=N
of the thiosemicarbazone moiety upon complexation.[35]
Bands in the range 404–436 cm−1 are assignable to ν(M–
N) frequencies.[36] The decrease in the stretching fre-
quency of C–S bond upon complexation indicates the
coordination via its thiolate sulfur.
3.3 | Description of crystal structures
3.3.1 | Crystal structure of
thiosemicarbazone
A colourless needle shaped crystals which are suitable
for X‐ray diffraction were obtained by the slow evapora-
tion
from
a
methanolic
solution
of
the
thiosemicarbazone. The compound crystallizes into a
monoclinic P21/c space group. The crystal data and
structure refinement parameters are shown in Table 1.
The ORTEP diagram for thiosemicarbazone is given in
Figure 1. The condensation between aldehyde and
thiosemicarbazide is evident from the azomethine bond,
C(7)–N(1) bond length of 1.272(2), which is near to the
reported C=N bond length (1.276(3) Å). The C(8)–S(1)
bond length is 1.6781(19) Å and C(8)–N(2) bond length
is 1.364(2) Å which are closer to the reported C=S and
C–N bond lengths [41]. These values suggested that the
compound thiosemicarbazone exists in thio‐amido form
in the solid state. The E conformation of the compound
with respect to C(7)–N(1) is derived from the torsion
angle C(6)–C(7)–N(1)– N(2),179.82(17)°. With respect to
N(1), the thiol sulfur S(1) lies trans and N(3) lies cis
which is.
3.2 | Electronic spectra
The electronic spectrum of the H2dsct was recorded in
10−5 M solution of DMF. The electronic spectra gave clear
evidence of characteristic absorptions of aromatic groups
as well as non‐bonded electrons in the complex. The
bands at 310 and 340 nm in the thiosemicarbazone deriv-
ative are due to π → π* and n → π* transitions.[37] This
evident from the N(1)–N(2)–C(8)–S(1) and N(1)–N(2)–
C(8)–N(3) torsion angles 179.27(15) and 0.9(3)°

6 of 14
MATHEWS ET AL.
TABLE 1 Crystallographic data and structure refinement for H2dsct, 1, 2 and 3 complexes
Parameters
H2dsct
[Zn(dsct)(phen)]·DMF [Zn(dsct)(bipy)]·DMF [Cu(dsct)(bipy)]·DMF
(1)
(2)
(3)
Empirical formula
Formula weight
Crystal system
Space group
Cell parameters
a (Å)
C14H16Cl2N3O S
345.26
C55H53Cl4N11O3S2 Zn2
C27H30Cl2N6O2SZn
C27H29Cl2CuN6O2 S
636.06
1252.74
Triclinic
Pī
638.92
Triclinic
Pī
Monoclinic
P21/c
Monoclinic
P21/n
14.3350(9)
6.1371(3)
17.8397(11)
90
10.6525(6)
9.8534(9)
18.5996(10)
75.961(3)
87.303(3)
73.516(3)
2761.3(3)
2
11.9910(13)
16.209(2)
17.411(2)
62.524(5)
87.233(6)
87.012(6)
2997.2(6)
4
16.0975(16)
11.8316(10)
17.5066(17)
90
b (Å)
c (Å)
α (°)
β (°)
93.154(3)
90
116.759(3)
90
γ (°)
Volume V (Å3)
1567.08(16)
4
2977.2(5)
4
Z
Calculated density
1.459
1.507
1.416
1.419
(ρ) (Mgm−3
)
Crystal size (mm3)
θ range for data collection
Limiting indices
0.300 x 0.250 x 0.250
2.759 to 28.310°
0.350x0.300x0.300
1.129 to 28.430°
0.35 x 0.30 x 0.30
1.319 to 28.347°
0.35 x 0.30 x 0.30
2.606 to 28.332°
−19 ≤ h ≤ 19,
−7 ≤ k ≤ 8,
−23 ≤ l ≤ 23
−14 ≤ h ≤ 13,
20 ≤ k ≤ 20,
24 ≤ l ≤ 21
−15 ≤ h ≤ 16,
21 ≤ k ≤ 21,
22 ≤ l ≤ 23
−20 ≤ h ≤ 21,
12 ≤ k ≤ 15,
23 ≤ l ≤ 23
Reflections collected/Unique
Reflections
18524/3893 [R
(int) = 0.0311]
33530/13603 [R
(int) = 0.0312]
21234/14988 [R
(int) = 0.0383]
35415/7431 [R
(int) = 0.0368]
Completeness to θ
25.242(99.9%)
25.242 (99.3%)
25.242 (97.2%)
25.242 (99.9%)
Maximum and Minimum
transmission
0.872 and 0.844
0.8030 and 0.7740
0.8030 and 0.7740
0.7500 and 0.7180
Goodness‐of‐fit on F2
1.012
0.986
0.966
1.074
Final R indices [I > 2σ (I)]
R1 = 0..0393,
wR2 = 0.1107
R1 = 0.0432,
wR2 = 0.1107
R1 = 0.0654,
wR2 = 0.1635
R1 = 0.0465,
wR2 = 0.1133
R indices (all data)
R1 = 0.0551,
wR2 = 0.1226
R1 = 0.0802,
wR2 = 0.1320
R1 = 0.1512,
wR2 = 0.2076
R1 = 0.0803,
wR2 = 0.1387
Largest difference peak
0.769 and 0.224
0.687 and − 0.638
0.842 and − 0.889
0.681 and − 0.445
and hole (e Ǻ−3
)
R1 = Σ||Fo|‐|Fc||/Σ|Fo|
wR2 = [Σw (Fo2‐Fc2)2/Σw (Fo2)2]1/2
respectively. Selected bond lengths and bond angles of the
thiosemicarbazone derivative and its complexes are given
in Table 2.
The special packing of the thiosemicarbazone is
assisted by the self‐assembly of the molecules which is
aided by the intramolecular hydrogen bonding which is
shown in Figure S2 and C–H···π interactions which
arranges the molecule in to a zig‐zag manner in a unit cell
(Table S3). The arrangement of atoms in the molecules
give rise to only one intramolecular hydrogen bonding
N(2)–H(2)···O(1) with D–A distance of 3.024(2) Å
(Table S2). The packing of molecules is further facilitated
by C(3)–H(3)–Cg(1) interaction with H···Cg distance of
2.82 Å (Figure S3).
The asymmetric unit of [Zn(dsct)(phen)]·DMF (1),
consists of two unique molecules, 1 and 2, with only slight
differences in bond distances and angles between them.
DMF molecule is present outside the coordination sphere
(Figure 2). The structure of the complex shows that com-
plexation was occurred by a thione to thiol tautomerism.

MATHEWS ET AL.
7 of 14
FIGURE 1 ORTEP representation showing the atom labelling of
non‐hydrogen atoms of the thiosemicarbazone (H2dsct).
Displacement ellipsoids are drawn at 30% probability
FIGURE 2 ORTEP representation showing the atom labelling of
the complex [Zn(dsct)(phen)]•DMF(1)
zinc via the imine nitrogen, the phenolic oxygen, thiolate
sulfur atoms, and two nitrogen atoms of the 1,10‐
phenathroline. To determine the degree of deviation from
square pyramid or trigonal bipyramid geometry the
It is accompanied by double deprotonation of the thiol sul-
fur and hydroxyl oxygen atoms in the thiosemicarbazone.
Therefore, it was doubly deprotonated and coordinated to
TABLE 2 Selected bond lengths (Å) and bond angles (°) of thiosemicarbazone and its complexes
Bond length (Å)
H2dsct
[Zn(dsct)(phen)]·DMF (1)
[Zn(dsct)(bipy)]·DMF (2)
[Cu(dsct)(bipy)]·DMF (3)
N(1)–N(2)
C(8) –S(1)
C(7) –N(1)
C(8) –N(2)
1.366(2)
1.6781(19)
1.272(2)
1.364(2)
N(1)–N(2)
C(8)–S(1)
1.383(3)
1.751(3)
1.278(3)
1.320(3)
2.084(2)
2.159(2)
2.120(2)
N(1)–N(2)
C(8)–S(1)
C(7)–N(1)
C(8)–N(2)
N(1)Zn(1)
N(4)–Zn(1)
N(5)–Zn(1)
1.395(6)
1.755(5)
1.282(6)
1.291(7)
2.084(4)
2.106(4)
2.123(4)
N(1)–N(2)
C(8)–S(1)
1.405(3)
1.756(3)
1.290(4)
1.317(4)
1.950(2)
2.235(2)
2.013(2)
C(7)–N(1)
C(8)–N(2)
Zn(1)–N(1)
Zn(1)–N(4)
Zn(1)–N(5)
C(7)–N(1)
C(8)–N(2)
N(1)–Cu(1)
N(4)–Cu(1)
N(5)–Cu(1)
Bond Angle (°)
H2dsct
[Zn(dsct)(phen)]·DMF(1)
[Zn(dsct)(bipy)]·DMF(2)
117.0(4)
[Cu(dsct)(bipy)]·DMF(3)
115.4(2)
C(7)–N(1)–N(2)
C(8)–N(2)–N(1)
C(8)–N(3)–C(9)
N(3)–C(8)–N(2)
N(3)–C(8)–S(1)
N(2)–C(8)–S(1)
115.93(16)
C(7)–N(1)–N(2)
C(8)–N(2)–N(1)
C(8)–N(3)–C(9)
N(2)–C(8)–N(3)
N(3)–C(8)–S(1)
N(2)–C(8)–S(1)
N(1)–Zn(1)–S(1)
N(1)–Zn(1)–N(4)
N(5)–Zn(1)–N(4)
N(4)–Zn(1)–S(1)
O(1)–Zn(1)–N(1)
O(1)–Zn(1)–N(5)
N(1)–Zn(1)–N(5)
O(1)–Zn(1)–N(4)
O(1)–Zn(1)–S(1)
N(5)–Zn(1)–S(1)
116.6(2)
112.4(2)
124.7(2)
117.7(2)
115.0(2)
127.3(2)
82.26(6)
174.38(9)
78.15(9)
101.51(6)
89.10(8)
110.18(9)
96.67(9)
90.65(8)
139.15(7)
110.45(6)
C(7)–N(1)–N(2)
C(8)–N(2)–N(1)
C(8)–N(3)–C(9)
N(2)–C(8)–N(3)
N(3)–C(8)–S(1)
N(2)–C(8)–S(1)
N(1)–Zn(1)–S(1)
N(1)–Zn(1)–N(4)
N(4)–Zn(1)–N(5)
N(4)–Zn(1)–S(1)
O(1)–Zn(1)–N(1)
O(1)–Zn(1)–N(5)
N(1)–Zn(1)–N(5)
O(1)–Zn(1)–N(4)
O(1)–Zn(1)–S(1)
N(5)–Zn(1)–S(1)
C(7)– N(1)–N(2)
C(8)–N(2)–N(1)
C(8)–N(3)–C(9)
N(2)–C(8)–N(3)
N(3)–C(8)–S(1)
N(2)–C(8)–S(1)
N(1)–Cu(1)–S(1)
N(1)–Cu(1)–N(4)
N(5)–Cu(1)–N(4)
N(4)–Cu(1)–S(1)
O(1)–Cu(1)–N(1)
O(1)–Cu(1)–N(5)
N(1)‐Cu(1)‐N(5)
O(1)–Cu(1)–N(4)
O(1)–Cu(1)–S(1)
N(5)–Cu(1)–S(1)
120.65(16)
124.95(16)
115.59(17)
125.14(15)
119.27(14)
111.9(4)
112.4(2)
123.9(3)
120.0(3)
115.3(2)
124.6(2)
84.45(7)
97.17(9)
77.28(8)
105.53(7)
93.48(9)
90.09(9)
174.00(9)
103.71(10)
150.72(8)
94.78(7)
124.7(2)
118.3(5)
113.7(4)
127.9(5)
81.45(13)
99.47(15)
77.46(15)
110.82(12)
89.46(16)
92.92(16)
176.66(16)
2.05(17)
137.07(13)
98.35(13)

8 of 14
MATHEWS ET AL.
derivative (Figure S4). A significant π… π interactions
strengthen the molecular chain by the interaction between
the pyridyl ring and phenyl ring of two adjacent molecules
with the centroid–centroid distances of 3.6355 Å of the cor-
responding interacting rings which is shown in Figure S5.
The compound 2 is crystallized in triclinic Pī space
group. The molecular structure of crystal [Zn(dsct)
(bipy)]·DMF (2) with atom numbering scheme is given in
Figure 3. The asymmetric unit consist of two zinc (II)
atom, two dianionic ligand moiety, two bipy and two
DMF molecule. No lattice water molecule is present in
the crystal system 3.
β − α
60
trigonality index, τ =
, was calculated, wherein β and
α are the two largest bond angles around the zinc atom.[42]
For an ideal square pyramidal geometry τ = 0 and for per-
fect trigonal bipyramidal geometry τ = 1. The τ values
found here are 0.5871 for Zn1 and 0.4236 in Zn2 indicate
the irregular coordination geometry along the pathway of
distortion to trigonal pyramidal. The non‐linear trans bond
angles, N(1)– Zn(1)–N(4) 174.38(9)°, N(5)–Zn(1)–S(1)
110.45(6)° and the bite angles N(4)– Zn(1)–S(1), 101.51
(6)°, N(1)–Zn(1)–S(1), 82.26(6)°, O(1)–Zn(1)–N(1),89.10
(8)°, O(1)–Zn(1)–N(5), 110.18(9)°, N(5)–Zn(1)–N(4), 78.15
Each Zn(II) atom is five coordinated by one oxygen
atom, one sulfur atom, one nitrogen atom from ligand moi-
ety and two nitrogen atom from the bipyridine. The C–S
bond length increases from 1.6781(19) Å to 1.755(5) Å in
[Zn(dsct)bipy]·DMF (2). After deprotonation the N2– C8
bond length also changes from 1.364(2) Å to 1.291(7) Å
due to the enolization of the ligand for coordination.
For Zn1 the complex gives a value of τ = 0.659 and for
Zn2 a value of 0.649 for angular structural parameter,
thereby confirming the distortion of the trigonal bipyrami-
dal geometry in the complex. It is also evident from the
(9)° also support the distorted geometry.
In this complex the ring puckering analysis and least
square plane calculation show that the ring Cg(1), com-
prising of the atoms Zn(1), S(1), C(8), N(2) and N(1), is
puckered with puckering amplitude Q(2) = 0.3002 Å
and Φ(2) = 359.4359°. Pseudorotation parameter P and
τ
m of the five membered metallocycle was also calculated,
and it was found that the metallocycle adopts envelope
conformation with P = 153.7° and τm = 23.2° for refer-
ence bond Zn(1)–S(1) in Cg(1) [32,33]. The ring Cg(3)
and Cg(7), comprising of atoms Zn(1), O(1), C(1), C(6),
C(7), N(1) in Cg(3) and C(9), C(10), C(11), C(12), C(13),
C(14) in Cg(7) are also found to be puckered with
puckering amplitude Q = 0.3471 Å, Θ = 115.80° and
Φ = 184.7091° for Cg(3) and Q = 0.5552 Å,Θ = 0.72 °
and Φ = 163.5292° for Cg(7).
The molecules are connected in the crystal lattice by
various intramolecular and intermolecular hydrogen
bonding interactions (Table S3). These hydrogen‐bonding
interactions have considerable result upon the structural
as well as spectral properties of the thiosemicarbazone
bond angles N1–Zn1–N5
= 176.66(16)°, O1–Zn1–
S1 = 137.07(13)°, N6–Zn2–N10 = 175.84(16)°, O2–Zn2–
S2 = 136.90(13). Ring puckering analysis and least square
plane calculations indicates that the ring Cg(1) consist of
Zn(1), S(1), C(8), N(2), N(1) is found to be puckered with
puckering amplitude Q(2) = 0.4063 Å, Φ(2) = 6.1637°.
The puckering of the above five membered metallocycle
was also calculated in terms of the pseudorotation parame-
ter P and τm and it was found that the P=166.5° and τ=30.1°
for reference bond Zn(1)–S(1) in Cg(1) [39,40]. The Cg(3)
comprising of O(1), C(1), C(6), C(7), N(1) and Cg(7) com-
prising of C(9),C(10), C(11), C(12), C(13), C(14) is also
found to be puckered in the complex. The puckering ampli-
tude Q=0.2687Å, Θ=117.42°, Φ=203.8887° for Cg(3) and
Q= 0.5732 Å, Θ=178.35°, Φ=46.1687° for Cg(7).
Conformational analysis show that this metallocycle Cg
(7) adopts the chair conformation.
The complex is driven by two classical hydrogen
bonding interactions where the proton attached to N3’
and N8’ are involved in an intermolecular hydrogen
bonding interactions with the O3 and O4 of the solvent
molecule (Figure S6). Two important π… π interactions
strengthen the molecular chain by the interaction
between the bipyridyl rings of two adjacent molecules
with the centroid–centroid distances of 3.7257 Å and
3.7419
Å
of the corresponding interacting rings
(Figure S7). Along with the π… π interaction, there are
C–H···π interactions where the protons interact
with the two six membered rings (Cg(6) and Cg(13))
(Table S6).
FIGURE 3 ORTEP representation showing the atom labelling of
the complex [Zn(dsct)(bipy)]•DMF(2). DMF molecule has been
omitted for clarity. Displacement ellipsoids are drawn at 30%
probability

MATHEWS ET AL.
9 of 14
TABLE 3 Antibacterial activity of the complexes and standard ampicillin towards various bacteria
Zone of inhibition (mm)
Bacteria
H2dsct
Complex 1
Complex 2
Complex 3
Ampicillin
Escherichia coli
4
‐
8
6
‐
4
3
‐
8
12
‐
7
6
Salmonella typhi
Enterobacter aerogenes
Shigella dysentriae
Bacillus cereus
3
2
‐
6
‐
‐
‐
12
19
17
‐
‐
‐
Staphylococcus aureus
‐
‐
‐
‐
TABLE 4 Docking interactions of the compound with 1m17 and 3hb5 proteins
Docking Score
(kcal/mol)
Hydrogen bonding
interactions
Compound
Electrostatic/hydrophobic interactions
PDB ID:1m17
H2dsct
−7.0
−8.9
ASP831
LEU820,LEU694,ALA719,VAL702,MET769
[Zn(dsdt)(bipy)]·DMF
ASP831, S1–N5
LEU694,VAL702,ALA719,LYS721,CYS773,ARG817
[Cu([Cu (dsdt)(bipy)]·DMF −9.6
‐
ASP776,ASP831,PHE699,ALA719,MET769,LEU820,
PHE699, CYS773, ARG817
PDB ID: 3hb5
Ligand H2dsct
−8.4
ASN152, TYR218
PHE192,PRO187,TYR155,VAL143,HIS221,VAL225,
VAL196,MET193
[Zn(dsct)(bipy)]·DMF
[Cu(dsct)(bipy)]·DMF
−8.9
−8.9
GLY92, S1–N5
ARG37, S1–N5
ILE14,ALA91,ARG37,ALA191,PHE192,LEU93,VAL113
LYS195, LEU93, VAL196, PHE192, ALA191
DMF. The compound is monoclinic with P21/n space
group. It is a five coordinated mononuclear complex.
DMF molecule is present outside the coordination sphere.
The trigonality index τ = 0.38 (where β = N(1)–Cu(1)–N
(5) = 174.00(9)° and α = O(1)–Cu(1)–S(1) = 150.72(8)°).
The differences in Cu–N bond distances N(1)–Cu
(1) = 1.950(2) Å, N(4)–Cu(1) = 2.235(2) Å, N(5)–Cu
(1) = 2.013(2) Å indicate variations in the strengths of the
bonds of coordinated nitrogen atoms. No classical hydro-
gen bonding is present in this compound. The various C–
H bonds are forming hydrogen bonding with the sulfur
and chlorine atom at a distances of 2.87, 2.92, 2.79 Å
(Figure S8). There exist strong C–H···π interactions
between these metal containing chelate rings Cg(6) and
Cg(3) with methyl protons and pyridyl ring protons
(Table S7). Also significant C‐H···π interactions are
observed with Cg(6) to the protons in the solvent molecule
as well (Figure S9) 4
The molecular structure of the compound, [Cu(dsct)
(bipy)]·DMF (3) along with the atom numbering scheme
is represented in Figure 4 and selected bond lengths and
bond angles are summarized in Table 4. Suitable pale yel-
low crystals were obtained from recrystallization from
3.4 | Antimicrobial activity
The ligand (H2dsct) and its metal complexes were screened
against the bacterial strains Escherichia coli, Salmonella
typhi, Enterobacter aerogenes, Shigella dysentriae, Bacillus
FIGURE 4 ORTEP plot of [Cu(dsct)(bipy)]•DMF (3) along with
atom numbering scheme of the non‐hydrogen atoms.
Displacement ellipsoids are drawn at 30% probability

10 of 14
MATHEWS ET AL.
[45]
cereus, Staphylococcus aureus. The zone of inhibitions are
compared with standard antibacterial drug ampicillin.
The results suggested that the complexes [Zn(dsct)
(phen)]·DMF (1), [Zn(dsct)(bipy)]·DMF (2) and [Cu(dsct)
(bipy)]·DMF (3) showed activity against E. Coli and Salmo-
nella typhi whereas the ligand gave activity against
Escherichia coli, Enterobacter aerogenes, Salmonella typhi
and Shigella dysentriae. The antimicrobial activity of
H2dsct ligand and its complexes is summarized in Table 3
. Complexes 1 and 3 showed higher activity against bacte-
rial strain, Escherichia coli than the reference drug
(Ampicillin). Complex 3 showed remarkable activity
against Salmonella typhi as compared to the standard drug.
The minimum inhibitory concentration was evaluated by
Muller Hinton broth method. It is the lowest concentration
at which the complete inhibition of microorganism occurs.
In this technique, different concentrations of complexes
were inoculated with the bacterial culture which showed
promising results. A positive control with culture and with-
out complexes and a negative control without inoculating
the culture but with complexes are maintained through-
out. For H2dsct, Escherichia coli gave 0.4 mg/ml, Enterobac-
ter aerogenes gave 0.6 mg/ml and Shigella dysentriae gave
0.9 mg/ml. For complexes 1, 2 and 3, E. Coli gives, 0.3,
0.4, 0.6 mg/ml respectively and Salmonella typhi gives,
0.4, 0.5,0.8 mg/ml.
explained on the basis of chelation theory
which says
that the increasing lipophilic nature of these complexes
resulting from the metal chelation is responsible for the
activity. In the chelate ring, the electron delocalization
increases which increases the lipophilic character of the
metal chelate. The antibacterial activity of complexes are
also related to the existence of 1,10‐phenathroline and
bipyridine as potential intercalator. The existence of such
planar aromatic heterocycles impart the complexes with
the opportunity to insert into the grooves of the double‐
helical DNA causing damage.[46] The results from the com-
plexes studied are consistent with those reported data for
the biological activities in other copper(II) and zinc(II)
complexes.[47,48] Killing of the microbes or inhibiting their
multiplication by blocking their active sites can be reasons
for their antibacterial activity.
F5-F10
3.5 | Molecular docking studies
The thiosemicarbazone and the two complexes were eval-
uated for the inhibition of tyrosine kinase activity of
EGFR and breast cancer mutant 3hb5‐Oxidoreductase
using the molecular docking method. Various interac-
tions such as π‐alkyl interaction, π‐π interaction, π‐donor
hydrogen bond interaction and conventional hydrogen
bond interaction through which ligands are binding to
the protein molecule. The binding mode of compounds
with the corresponding protein are shown in
Figure 5–10. Docking interactions are given in Table 4.
The azomethine (>C=N) group in the complexes have
the potential to form hydrogen bonds with active centres
within the cell that cause harm for the normal cell func-
tioning and can lead to the killing of the bacteria or
inhibiting their multiplication.[43,44] The activity can be
FIGURE 5 Interaction of 1 m17 on
H2dsct
FIGURE 6 Interaction of 1 m17 on [Zn
(dsct)(bipy)]•DMF

MATHEWS ET AL.
11 of 14
FIGURE 7 Interaction of 1 m17 on [Cu
(dsct)(bipy)]•DMF
FIGURE 8 Interaction of 3bh5 on
H2dsct
FIGURE 9 Interaction of 3hb5 on [Zn
(dsct)(bipy)]•DMF
FIGURE 10 Interaction of 3hb5 on [Cu
(dsct)(bipy)]•DMF

12 of 14
MATHEWS ET AL.
TABLE 5 In vitro cytotoxicity of Cu(II) complex against MCF‐7 cancer cell line
Sample Concentration (μg/ml)
OD value I
OD value II
OD value III
Average OD
Percentage Viability
Control
6.25
12.5
25
0.8071
0.3559
0.2854
0.1957
0.1763
0.1616
0.7936
0.3562
0.2836
0.1983
0.1711
0.1606
0.7954
0.3597
0.2826
0.1871
0.1725
0.1624
0.7987
0.3573
0.2839
0.1937
0.1733
0.1615
100.00
44.73
35.54
24.25
21.70
20.22
50
100
FIGURE 11 Phase contrast images
3.5.1 | Molecular docking analysis with
1 m17 protein
the OH of ASNX: 152 to the amino group of the
thiosemicarbazone with 2.13 Å and the second hydrogen
bonding interaction is between the oxygen of TYRX: 218
to the OH group of salicylaldehyde derivative. The com-
pound [Zn(dsct)(bipy)]·DMF showed two hydrogen
bond interaction with ASP831 and an intramolecular
hydrogen bonding. The first hydrogen bond is between
the NH of GLY92 with the N2 position of the compound
with a distance of 2.31 Å and the other one is within
the complex. In the [Cu(dsct)(bipy)]·DMF complex also
there are two conventional hydrogen bond interactions
present with ARG37 and an intramolecular hydrogen
bonding. The distance of the interaction between
ARG37 to the S1 of the compound is 2.81 Å. The results
confirm that complex [Cu (dsct)(bipy)]·DMF showed
efficient inhibition against 1 m17 and 3hb5 cancer cell
lines and are having highest docking score as compared
The synthesized thiosemicarbazone and the metal com-
plexes were docked with 1 m17 tyrosine kinase protein.
The thiosemicarbazone (H2dsct) have formed one hydro-
gen bonding interaction with ASP831. The hydrogen
bond was identified between NH of thiosemicarbazone
and ASP831 and the distance was found to be 2.91 Å.
The [Zn(dsct)(bipy)]·DMF (2) had formed two hydrogen
bond interaction with ASP831 and a hydrogen bonding
within the molecule. The first hydrogen atom is observed
between OH of ASP831 with the C1–S1 bond of the
complex and the distance was found to be 3.60 Å. The
[Cu (dsct)(bipy)]·DMF (3) didn't show any hydrogen bond
interaction with the active site of 1 m17 but the docking
score is high indicating the importance of electrostatic
and hydrophobic interactions shown by the compound
with the active site of the protein. Among all the com-
plexes synthesized, compound 3 showed highest docking
score of −9.6 kcal/mol, which is higher than what is
reported in literature.
[49,50]
to reported ones.
3.6 | Anticancer activity
Preparation of metal based anticancer drug is very impor-
tant as they have proved to have anticancer activity. The
compound [Cu(dsct)(bipy)]·DMF is screened for their
anticancer activity against breast cancer cell line
(MCF‐7) at a concentration of 100 μg/ml. The LC50 values
of the compound was measured by using different con-
centrations (5, 12.5, 25, 50 μg/ml). The complex showed
an LC50 of 6.25 μg/ml. Furthermore, the compound was
also screened against normal L929 (Mouse Fibroblast)
cells line. The LC50 was found to be 218.338 μg/ml. Thus
3.5.2 | Molecular docking analysis with
3hb5 protein
The thiosemicarbazone (H2dsct) has a better binding
interaction with the breast cancer mutant 3hb5‐
oxidoreductase and in it exhibited binding energy of
−8.4 kcal/mol along with 2 hydrogen bonding interac-
tions. The first hydrogen bonding interaction is between

MATHEWS ET AL.
13 of 14
the compound [Cu(dsct)(bipy)]·DMF, behaved as the
most active and effective complex which can be used as
an anticancer drug for breast cancer. The presence of
azomethine group in the chelate ring may be the reason
for its higher activity. When metal coordinated with the
azomethine nitrogen in the chelate ring, the polarity
reduces and increases the π‐electron delocalization in
the ligand moiety. Thus the entry through the lipid layer
of cell membranes becomes more enhanced. The results
can also be compared with literature, which shows that
the compound is more efficient than what is reported
already in the literature.[51] (Table 5) (Figure 11)
ACKNOWLEDGEMENTS
Nimya Ann Mathews acknowledges the University Grants
Commission, New Delhi, India for the award of a Junior
Research Fellowship. The authors are thankful to the
Sophisticated Analytical Instrumentation Facility, Cochin
University of Science and Technology, Kochi, India for ele-
mental analyses, NMR spectra and single crystal X‐ray dif-
fraction measurements. They are also grateful to Biogenix
Research Center, Thiruvanathapuram for anticancer
activity studies.
ORCID
M.R. Prathapachandra Kurup
https://orcid.org/0000-
0002-9434-890X
4 | CONCLUSION
REFERENCES
In this paper we have described the synthesis of zinc(II)
and copper(II) complexes with an ONS donor
thiosemicarbazone. The complexes were characterized by
spectral studies. The molecular structures of H2dsct, Zn
(II) and Cu(II) complexes were confirmed by SCXRD anal-
ysis. In the complexes, thiosemicarbazone exists in the
thioiminolate form and acts as dideprotonated tridentate
ligands coordinating through phenolic oxygen,
thioiminolate sulfur and azomethine nitrogen. In the ana-
lyzed complexes hydrogen bonding interactions and vari-
ous nonbonding interactions played a principal role in
the crystal network formation. The synthesized
thiosemicarbazone and its complexes, had a satisfactory
result for their antibacterial activity against bacterial spe-
cies. All the complexes showed activity against bacterial
strains E.coli and Salmonella typhi. The thiosemicarbazone
showed activity against three bacterial strains such as E.
coli, Enterobacter aerogenes and Shigella dysentriae. Com-
plex 2 showed very good activity as compared to standard
drug (Ampicillin) against the bacterial strain, Salmonella
typhi. Molecular docking acted as an additional tool for
pharmacophore‐based virtual screening to make the dis-
covery of potent EGFR TK inhibitors and breast cancer
mutant more efficient. Among the compounds that are
screened, [Cu (dsct)(bipy)]·DMF gave very good docking
score − 9.6 kcal/mol for 1 m17 cell line. [Cu (dsct)
(bipy)]·DMF and [Zn (dsct)(bipy)]·DMF, both gave the
same docking score of −8.9 kcal/mol for the 3hb5 cell line.
The in vitro cytotoxic studies against breast cancer cell line
(MCF‐7) and normal L929 cell line revealed that the Cu (II)
complex is a promising good anticancer agent and had the
LC50 of 6.25 μg/ml. So the compound can be considered as
important and effective drug against breast cancer. Thus
the above study could be useful for the in vivo studies and
can be the foundation stone for its applications in the field
of drug development.
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