Microwave-assisted synthesis, biological evaluation and molecular docking studies of new coumarin-based 1,2,3-triazoles

Article abstract of DOI:10.1039/d0ra01052a

Coumarin-based 1,4-disubstituted 1,2,3-triazole derivatives were synthesized using a highly efficient, eco-friendly protocol via a copper(i)-catalyzed click reaction between various substituted arylazides and terminal alkynes. The synthetic route was easy

Full text of DOI:10.1039/d0ra01052a

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Microwave-assisted synthesis, biological evaluation
and molecular docking studies of new coumarin-
Cite this: RSC Adv., 2020, 10, 11615
based 1,2,3-triazoles†
a
Ravinder Dharavath,a Nalaparaju Nagaraju,a M. Ram Reddy,a D. Ashok,
*
M. Sarasija,b M. Vijjulatha,c Vani T,c K. Jyothid and G. Prashanthid
Coumarin-based 1,4-disubstituted 1,2,3-triazole derivatives were synthesized using a highly efficient, eco-
friendly protocol via a copper(I)-catalyzed click reaction between various substituted arylazides and
terminal alkynes. The synthetic route was easy to access and gave excellent yields under microwave
irradiation conditions compared to the conventional heating route. The structures of all the compounds
were characterized by IR, 1H NMR, 13C NMR spectroscopy and mass spectrometry. All the synthesized
compounds were screened for their in vitro antimicrobial, antioxidant and anti-inflammatory activities;
among all compounds, 8a, 8j, 8k and 8l exhibited better results with respect to standard drugs.
Furthermore, molecular docking studies have been carried out with PDB IDs 2VCX (anti-inflammatory),
Received 4th February 2020
Accepted 24th February 2020
3VXI (antioxidant), 4GEE (antimicrobial) and 2XFH (antifungal) using the Glide module of the Schrodinger
¨
suite. The final compounds 8d, 8e, 8h, and 8k showed the highest hydrogen bond interactions with His-
DOI: 10.1039/d0ra01052a
rsc.li/rsc-advances
88 and Val-191 proteins and with water in all the proteins.
gastrointestinal risks.4 Although several drugs exist in the
market, there is a serious need to required for the development
1. Introduction
of new antimicrobial drugs and NSAID (Nonsteroidal Anti-
Inammatory Drugs).
In spite of the extensive use of antibiotic and vaccination
programs, infectious diseases continue to be a primary cause of
morbidity and mortality worldwide. The continued emergence
of antibiotic resistance is one of the utmost global health
threats.1 Multidrug resistant bacterial infections are increasing
in frequency and require the use of more aggressive antibiotic
therapies.2 While the continued development of novel antibi-
otics is crucial, alternative strategies are also needed, such as
the development of adjuvants that target bacterial pathways
responsible for antibiotic tolerance or resistance.3 Inamma-
tion is a general condition that occurs during infections in
many number of diseases from hay fever, periodontitis,
atherosclerosis, rheumatoid arthritis to cancer. The generally
used non-steroidal anti-inammatory drugs (NSAIDs) provide
analgesic and antipyretic effects in addition to anti-
inammatory effects in higher doses. The therapeutics are
prevailing, but they seriously increase vascular and
The chemistry of heterocyclic compounds has been an inter-
esting eld of study for a long period. Coumarin belongs to the
class of avonoids and are found in many natural as well as
synthetic products. Coumarin, a well-known structural motif,
shows many pharmacological activities such as anticancer,5 anti-
oxidant,6 anti-inammatory,7 antimicrobial,8 and anticoagulant9
effects; it is also proved to be a promising anti-acetylcholines-
terase10 agent. Some of the marketed drugs like Warfarin,9 Phen-
procoumon,10 Psoralen11 and Angelicin12 contain the coumarin
skeleton in their structure and are found to exhibit various phar-
macological activities (Fig. 1). Coumarins can be synthesized by
using the Perkin,13,14 Pechmann15,16 and Knoevenagel17 reactions.
Among the coumarin compounds, the 3-aryl substituted couma-
rins have gained attention due to their biological activities such as
antimicrobial, antioxidant and anti-inammatory activities. The 3-
aryl coumarin derivatives can be synthesized by using reagents
such as DCC, DDQ, NaOH, POCl3 and Mukaiyama reagent (2-
chloro-1-methylpyridiniumiodide).18,19 Many of these methods
suffer limitations such as the formation of a complex mixture of
products, usage of excess reagents and longer reaction times with
poor yields. For this reason, a relatively more viable reagent such
as 1,1-carbonyldiimidazole20,21 (CDI) is used for the synthesis of 3-
aryl coumarin derivatives, which provides excellent yields by
avoiding all the above-mentioned issues. On the other hand 1,2,3-
triazole, an important heterocyclic motif, has gained much
aGreen and Medicinal Chemistry Lab, Department of Chemistry, Osmania University,
Hyderabad-500007, India. E-mail: ashokdou@gmail.com
bDepartment of Chemistry, Satavahana University, Karimnagar-505001, India
cMolecular Modelling and Medicinal Chemistry Group, Department of Chemistry,
Osmania University, Hyderabad-500007, India
dDepartment of Pharmaceutical Chemistry, St Mary's College of Pharmacy,
Secunderabad-500025, India
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d0ra01052a
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Fig. 1 Marketed drugs containing coumarin and 1,2,3-triazole.
importance in medicinal chemistry and attracted much attention friendly and easy to carry out. The rate of reaction is
from organic chemists due to its exceptional pharmacological enhanced due to thermal/kinetic effects, which are signicance
activities such as antimicrobial,22–24 anticancer,25–29 anti-HIV30 and of high temperatures that can be quickly attained when the
antitubercular activities.31 Some of the important drugs like TSAO reaction mixture is exposed to a microwave eld.
and Tazobactam contain 1,2,3-triazole in their structure (Fig. 1).
Inspired by the diverse pharmacological activities of the
In addition, some of the coumarin-based 1,2,3-triazole coumarin and 1,2,3-triazole derivatives, we synthesized a series
(Fig. 2) compounds were reported with considerable anti-Alz- of coumarin-based 1,2,3-triazole compounds 8(a–l) using
heimer's,32 anticancer,33 and antibacterial activities34 and as conventional and microwave irradiation methods; they were
acetylcholinesterase inhibitors.35 The coumarin-based triazole then evaluated for their in vitro antioxidant, anti-inammatory,
compound 2H-chromen-2-one36 showed antimicrobial activity, and antimicrobial activities followed by molecular docking
3-[1-(4,5-dicarbomethoxy-1,2,3-triazoloacetyl)]coumarin37
showed antifungal activity and 2-chromene-3-carboxylate
derivative38 showed good antioxidant activities.
studies.
Computational biology and bioinformatics play a major
role in designing drug molecules and have the potential to
Microwave-assisted synthesis plays a signicant role in speed up the drug discovery process. Molecular docking of the
synthetic chemistry as it reduces the reaction time with drug molecules with the receptor (target) gives signicant
enhanced yields when compared to the conventional method information about drug–receptor interactions and is
and thus is known to be environmentally friendly.39,40 In view of frequently used to nd out the binding orientation of drug
the environmental effects, the microwave-assisted synthesis is candidates to their protein targets in order to calculate the
considered as an alternative for the conventional heating affinity and activity.39 In view of the pharmaceutical activities
method to approach green synthesis. This technique is also of two or more pharmacophore moieties, i.e., coumarin and
used in medicinal chemistry to develop drug molecules as it 1,2,3-triazole, in order to nd the combined effects of the
offers higher yields in a short reaction time and reduces the newly synthesized scaffolds on biological potency, we herein
waste products when compared to the conventional heating report a protocol for the design and synthesis of some
method. Moreover, these reactions are simple, clean, eco- coumarin-based 1,2,3-triazole compounds.
Fig. 2 Synthetic coumarin-based 1,2,3-triazoles reported as antifungal and antioxidant agents.
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Scheme 1 Synthetic route for coumarin-based 1,2,3-triazole compounds 8(a–l).
Finally, the reaction conditions were successfully optimized with
acid (1 eq.), CDI (1.2 eq.) using K2CO3 as the base and dry acetone
as the solvent under inert atmospheric conditions.
2. Results and discussion
2.1 Chemistry
The protocol for the synthesis of coumarin-based 1,2,3-triazoles
is depicted in Scheme 1. The rst step of the synthetic route
involves the activation of substituted phenyl acetic acid 1 by
Table
1 Comparison of the time and yields of the synthesized
compounds 6(a–d) and 8(a–l) using conventional and microwave
irradiation methods
using 1,1-carbonyldiimidazole
2 (CDI) using potassium
carbonate as the base and acetone as the solvent at room
temperature for 1 h to obtain the intermediate 3. In the second
step, the alkyne-substituted hydroxy acetophenone 5 is ob-
tained by the selective propargylation of 2,4-dihydrox-
yacetophenone 4 using K2CO3 in DMF and it is further treated
with the intermediate 3 under reux conditions for 4 h using
potassium carbonate and acetone to afford 3-aryl-substituted
coumarin compounds 6(a–d). Finally, the alkyne coumarin
intermediates 6(a–d) undergo copper(I)-catalyzed Huisgen
cycloaddition41 (click chemistry42–44) when treated with different
aryl azides 7(a–c) using copper iodide in the presence of DMF/
H2O (1 : 1) to obtain coumarin-containing 1,2,3-triazole title
compounds 8(a–l).
Initially, the activation of phenyl acetic acids was attempted
using DABCO as the coupling agent by using a procedure re-
ported in literature,45 but it could not give promising results.
Activation was then performed by treating an acid (1 eq.) with
DBU (1 eq.) as a base using two different solvents, namely,
dichloromethane and toluene by following a literature protocol.46
Microwave irradiation
method
Conventional method
Product
Time (h)
% yield
Time (min)
% yield
6a
6b
6c
6d
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
5
5.5
4
4.5
5
4.5
5
4.5
5.5
5
75
78
79
75
72
69
75
76
75
76
70
69
72
68
72
68
5
6
7
6
7
7
6
8
7
6
8
8
7
5.5
6
7
86
89
90
86
85
82
84
85
85
88
82
80
85
80
85
80
5
5.5
4.5
5
6
5.5
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Table 2 Optimization of compound 8a in various methods
2.2 Biological activity
All the synthesized compounds 6(a–d) and 8(a–l) were
screened for antioxidant, anti-inammatory and antimicrobial
scavenging activities. Among all the screened compounds 8a,
8j, 8k and 8l showed better results compared with standard
drugs.
Microwave
irradiation
method
Conventional
method
Entry
Solvent
(% yield)
(% yield)
1
2
3
4
5
THF
35
20
17
58
60
40
27
24
62
65
CH3CN
1,4-Dioxane
DMF
DMF/H2O
(7 : 3)
DMF/H2O
(3 : 2)
DMF/H2O
(1 : 1)
2.3 SAR studies
2.3.1 Antioxidant activity. The in vitro antioxidant47 activi-
ties of intermediates 6(a–d) and nal targets 8(a–l) were deter-
mined by using two methods, namely, the DPPH47 radical
6
7
68
72
75
85
scavenging assay and H2O2 scavenging assay method31 with
48
Ascorbic acid taken as the standard drug. All the synthesized
compounds, i.e., 6(a–d) and 8(a–l) were screened for in vitro
scavenging activity. The IC50 values ranged from 338.48 mM
mLÀ1 to À0.064 mM mLÀ1 compared with that of standard
Ascorbic acid (IC50 value 1.46 mM mLÀ1). Compounds 8k (IC50
value 0.06146 mM mLÀ1), 8j (IC50 value 1.11 mM mLÀ1) and 8d
(IC50 value 1.29 mM mLÀ1) showed excellent activity because the
presence of methoxy and other electron releasing groups like
methyl maintained the stability of the compounds and also
contributed to the improved activity for compound 8k. The
presence of two methoxy groups in compound 8d slightly
decreased the activity. Further substitution of electron-
withdrawing groups like chlorine and methoxy in compound
8l decreased the activity. In addition, 8a (3.50 mM mLÀ1), 8l (3.52
mM mLÀ1) and 8f (3.72 mM mLÀ1) exhibited good activity than
the standard drug in the DPPH method. In contrast, in the H2O2
method, compound 8k (IC50 value 0.06146 mM mLÀ1) exhibited
signicant results and 8j (IC50 value 1.29 mM mLÀ1), 8c (IC50
value 1.45 mM mLÀ1), 8f (IC50 value 1.72 mM mLÀ1) and 8a (IC50
value 1.76 mM mLÀ1) revealed good activity than standard
The syntheses of alkyne-substituted 3-aryl coumarin inter-
mediates 6(a–d) and coumarin-based 1,2,3-triazole nal
compounds 8(a–l) were carried out using both conventional and
microwave (MW) irradiation methods. Among the two methods,
the microwave irradiation method gave good yields (80–90%)
when compared to the conventional method (68–79%). The
reaction time and yields obtained for the intermediates 6(a–d)
and nal compounds 8(a–l) via both the methods are summa-
rized in Table 1.
The optimized reaction conditions for the synthesis of the
nal compounds 8(a–l) by the click reaction of different aryl
azides 7(a–c) with alkyne intermediates 6(a–d) using copper(I)
iodide as a catalyst under different solvent conditions in both
conventional and MW irradiation methods are tabulated in
Table 2. Among the reaction conditions performed, the best
results were achieved when DMF/H2O (1 : 1) was used as the
solvent system in both the methods.
Table 4 Anti-inflammatory activity of compounds 6(a–d) and 8(a–l)
Anti-inammatory
Table 3 Antioxidant activity of compounds 6(a–d) and 8(a–l)
Antioxidant activity
Egg-albumin
method IC50
Heat-induced
DPPH method IC50
(mM mLÀ1
H2O2 method IC50
(mM mLÀ1
hemolytic method
Compound
)
)
Compound
(mM mLÀ1
)
IC50 (mM mLÀ1
)
6a
6b
6c
6d
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
2.24 Æ 0.93
20.00 Æ 0.34
293.18 Æ 0.25
4.5 Æ 0.47
3.524 Æ 0.47
23.57 Æ 0.68
7.07 Æ 0.02
1.35 Æ 0.45
1.76 Æ 0.06
124.48 Æ 0.53
1.45 Æ 0.45
71.21 Æ 0.47
343.33 Æ 0.57
1.72 Æ 0.47
18.57 Æ 0.69
42.51 Æ 0.47
4.8 Æ 0.56
6a
6b
6c
6d
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
42.06 Æ 0.57
22.91 Æ 0.25
63.72 Æ 0.32
16.50 Æ 0.91
15.78 Æ 0.52
59.809 Æ 0.69
76.49 Æ 0.14
238.13 Æ 0.35
59.80 Æ 0.63
31.21 Æ 0.47
103.26 Æ 0.69
53.77 Æ 0.14
45.35 Æ 0.87
18.90 Æ 0.37
42.53 Æ 0.41
28.90 Æ 0.65
17.52 Æ 0.98
12.06 Æ 0.57
22.91 Æ 0.25
63.72 Æ 0.32
15.00 Æ 0.91
17.78 Æ 0.42
69.809 Æ 0.69
66.49 Æ 0.14
138.13 Æ 0.35
69.80 Æ 0.63
17.11 Æ 0.47
13.16 Æ 0.69
43.77 Æ 0.14
15.35 Æ 0.87
15.90 Æ 0.37
60.67 Æ 0.41
18.90 Æ 0.65
17.52 Æ 0.98
3.5 Æ 0.25
338.48 Æ 0.47
42.50 Æ 0.58
1.11 Æ 0.43
343.33 Æ 0.58
3.72 Æ 0.69
18.57 Æ 0.12
2.51 Æ 0.36
4.8 Æ 0.24
1.29 Æ 0.35
0.061 Æ 0.38
3.524 Æ 0.65
1.46 Æ 0.52
1.269 Æ 0.14
0.061 Æ 0.41
3.06 Æ 0.32
1.16 Æ 0.89
Ascorbic acid
Diclofenac
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Table 5 Antibacterial activity of compounds 6(a–d) and 8(a–l) at different concentrations
Zone of inhibition (mm)
Gram positive bacteria
Gram negative bacteria
Staphylococcus aureus
Bacillus subtilis
Escherichia coli
Klebsiella pneumonia
Compound
10 mg mLÀ1
20 mg mLÀ1
10 mg mLÀ1
20 mg mLÀ1
10 mg mLÀ1
20 mg mLÀ1
10 mg mLÀ1
20 mg mLÀ1
6a
6b
6c
6d
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
12
09
10
12
22
15
18
23
16
18
24
15
16
26
19
19
20
18
19
20
17
32
24
36
32
23
25
34
24
27
34
26
27
30
11
12
10
09
23
16
16
22
15
19
22
16
19
27
16
18
20
21
19
22
18
40
32
34
42
32
38
42
28
39
39
32
37
40
08
10
11
09
16
13
14
18
12
15
18
14
12
21
12
14
15
11
12
15
12
21
16
18
23
16
19
25
17
20
29
14
25
20
06
04
07
12
14
08
09
13
08
11
12
06
09
14
06
08
10
10
11
09
14
20
14
16
20
13
17
22
13
17
22
12
15
18
Gatioxacin
Ascorbic acid (IC50 value 1.16 mM mLÀ1). The antioxidant and 8i showed good activity against all bacterial strains due to the
activity values are shown in Table 3. electron-withdrawing groups on the coumarin ring. Compound 8k
2.3.2 Anti-inammatory activity. The in vitro anti-inam- and compound 8l both showed similar activity to that of the
matory49,50 activities of all the synthesized compounds 6(a–d) standard drug. The starting compounds 6(a–d) did not show
and 8(a–l) were determined by using two methods, namely, the activity. The results also demonstrated that the activity of these
egg-albumin method and heat-induced hemolytic method by compounds 6(a–d) and 8(a–l) was inuenced by their structures. In
taking Diclofenac as the standard drug. In the egg-albumin conclusion, 8a and 8j showed very high potential antibacterial
method, 8a (IC50 value 15.78 mM mLÀ1) and 6d (IC50 value activity against tested organisms.
16.50 mM mLÀ1) exhibited excellent activity than Diclofenac
(IC50 value 17.52 mM mLÀ1). In the heat-induced hemolytic
Table 6 Antifungal activities of the compounds 6(a–d) and 8(a–l) at
method, compounds 6a (IC50 value 12.06 mM mLÀ1), 8g (IC50
a concentration 50 mg mLÀ1
value 13.16 mM mLÀ1), 6d (IC50 value 15.00 mM mLÀ1), 8i (IC50
value 15.35 mM mLÀ1), 8j (IC50 value 15.90 mM mLÀ1) and 8f
(IC50 value 17.11 mM mLÀ1) exhibited excellent activity; also, 8a
Zone of inhibition (mm) at 50 mg mLÀ1
concentration
(IC50 value 17.78 mM mLÀ1) and 8l (IC50 value 18.90 mM mLÀ1
)
Aspergillus
avus
Fusariumoxy
sporum
demonstrated good activity compared to the standard Diclofe-
nac drug (IC50 value 17.52 mM mLÀ1). The anti-inammatory
activity values are shown in Table 4.
Compound
Aspergillus niger
6a
6b
6c
6d
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
07.2
08.8
07.2
08.2
18.8
17.9
18.2
10.6
13.6
15.2
10.3
14.6
15.9
18.6
16.5
15.9
17.3
06.4
07.2
08.6
07.9
17.6
16.8
16.3
11.8
14.2
14.8
12.5
13.8
14.5
16.7
15.8
14.8
16.4
07.3
06.6
09.2
06.5
18.6
17.8
18.9
11.6
14.8
16.2
12.6
14.6
15.8
19.0
16.2
14.3
18.2
2.3.3 Antibacterial activity. The newly synthesized
compounds 6(a–d) and 8(a–l) were screened for their antibacterial
activity against Gram-positive strains such as Staphylococcus aureus
(MTCC 96) and Bacillus subtilis (MTCC 121) and Gram-negative
strains such as Escherichia coli (MTCC 43) and Klebsiella pneu-
monia (MTCC 530) at various concentrations, i.e., 10 mg mLÀ1 and
20 mg mLÀ1 by using the agar disc diffusion method.51 The zone of
inhibition was measured in mm and Gatioxacin was used as the
standard drug; the results are shown in Table 5. From the biological
evaluation of the activity of the intermediates 6(a–d) to the nal
compounds 8(a–l), activity further increased due to the presence of
1,2,3-triazole moieties. Among all the prepared compounds, 8a, 8d,
8g and 8j were highly potent due to the presence of the methoxy
group in the triazole ring and also, compounds 8b, 8c, 8e, 8f, 8h
Clotrimazole
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Fig. 3 Docking pose images of intermediate compounds 6b and 6d showing H-bond interaction with water in Gram positive bacteria by the
protein 4GEE.
Fig. 4 Docking pose images of final compounds 8d, 8h and 8k showing H-bond interaction with His-88 in 2VCX protein (a), Val-191 in 3VXI (b)
and water in 2XFH and 4GEE proteins (c), respectively.
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2.3.4 Antifungal activity. All the synthesized compounds
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anti-inammatory activity since it is a prostaglandin D2 syn-
thase56 protein involved in the cyclooxygenase pathway.57 Simi-
larly, 3VXI was used for its anti-oxidant activity due to its dye
decolourising peroxidase (DyP) complex with Ascorbic acid as
the crystal ligand.58 The protein 4GEE was considered because
of its DNA–gyrase B and topoisomerase IV-mediated broad
spectrum activity.59 For the identication of antifungal activity,
we thereby considered 2XFH Cytochrome P450 EryK cocrystal-
lized with the inhibitor Clotrimazole.60 The potential binding
free energies (DG) were evaluated and the rationality of the
compounds was further evaluated through QikProp for their
drug likeness.
In conclusion, comparative docking studies from all the
proteins revealed that compound 8l showed a high docking
score of À7.792 and a binding energy of À117.95 in the protein
2VCX; also, their predicted activities were found to be slightly
higher than that of the standard (provided in the ESI Table†).
This clearly indicated that compound 8l showed an explicit
effect as a potential anti-inammatory, antimicrobial and
antioxidant molecule. The intermediate compounds 6b and 6d
showed best H-bond interactions with water in all the proteins
(2XFH, 4GEE and 3VXI) as the standard Ascorbic acid and
Gatioxacin predominantly (as illustrated in Fig. 1 and 3 of the
ESI†), stating that these compounds could be further exploited
to newer chemical agents possessing antioxidant and antimi-
crobial activities, as depicted in Fig. 4. The standard antifungal
agent Clotrimazole shows hydrogen bond interactions with Arg-
293 (depicted in Fig. 2 provided in the ESI†). The nal
compounds 8d, 8e, 8h and 8k showed hydrogen bond interac-
tions with His-88 (Fig. 4a) and Val-191 (4b) amino acids and
with water (4c) in all the proteins 2VCX, 3VXI, 4GEE and 2XFH.
6(a–d) and 8(a–l) were screened for their in vitro antifungal
activity against three fungal organisms, namely, Aspergillus niger,
Aspergillus avus and Fusariumoxy sporum at a concentration of
50 mg mLÀ1 by using the disc diffusion method51 and the results
were compared with that of Clotrimazole, used as a standard
drug. The study of antifungal activity is shown in Table 6; it was
observed that among all the synthesized compounds, 8a, 8b, and
8c showed better activity against the three pathogenic fungi due
to the presence of uorine group on coumarin. Compounds 8j,
8k and 8l showed better activity due to the presence of the
methoxy group in the triazole ring. The remaining compounds
exhibited similar activity to that of the standard drug. Due to the
methoxy group of the triazole compounds 8d and 8g, they
showed poor activity. It was observed that the intermediate-to-
product activity increased due to the presence of the 1,2,3-tri-
azole moiety. Overall, the antifungal activities of the compounds
were good against the tested fungal strains.
2.4 Molecular docking studies
To gain more insights into the interactions of coumarin-based
1,2,3-triazole derivatives 8(a–l), molecular docking studies
were performed. Molecular docking was carried out using the
¨
Glide module of the Schrodinger suite using PDB IDs 2VCX
(anti-inammatory),52 3VXI (antioxidant),53 4GEE (antimicro-
bial)54 and 2XFH (antifungal)55 to correlate the binding mode of
the synthesized compounds with the proteins. The above-
mentioned proteins were selected on the basis of the refer-
ence compound that existed as a co-crystal ligand on the target
protein. In the current work, we have considered 2VCX for its
Table 7 Quantified active site binding free energies along with the docking scores of the synthesized compounds and standard molecules
Docking scores
Binding free energies
Anti-microbial
Anti-microbial
Anti-inammatory Anti-oxidant
Anti-bacterial Anti-fungal Anti-inammatory Anti-oxidant
Anti-bacterial Anti-fungal
Compounds activity (2VCX)
activity (3VXI) (4GEE)
(2XFH)
activity (2CVX)
activity (3VXI) (4GEE)
(2XFH)
6a
6b
6c
6d
8a
8b
8c
8d
8e
8f
8g
8h
8i
8k
8l
À5.984
À6.315
À6.177
À6.232
À6.928
À6.587
À6.165
À6.962
À6.927
À6.051
À6.972
À6.725
À6.575
À6.587
À7.792
À5.553
—
À4.882
À4.826
À4.559
À3.801
À3.355
À3.636
À2.949
À2.438
À3.740
À3.528
À3.720
À3.778
À2.823
À3.240
À2.868
—
À5.760
À6.748
À6.585
À6.580
À5.756
À4.994
À5.122
À5.970
À5.796
À4.818
À5.554
À5.654
À5.659
À5.006
À4.869
—
À6.657
À5.148
À4.857
À4.791
À3.180
À4.096
À5.676
À2.927
À2.368
À4.339
À2.792
À3.594
À4.112
À2.587
À3.984
—
À83.72
À86.94
À86.36
À83.57
À94.07
À88.37
À88.66
À92.74
À92.26
À92.16
À106.36
À92.263
À94.63
À94.638
À117.95
À91.55
—
À54.41
À55.04
À55.68
À46.00
À52.26
À53.29
À59.42
À54.29
À60.44
À47.36
À57.00
À47.41
À53.35
À54.15
À50.68
—
À69.13
À70.79
À71.29
À78.56
À68.97
À57.01
À53.52
À71.94
À71.17
À62.39
À67.63
À72.09
À71.45
À62.72
À61.15
—
À77.31
À61.08
À61.61
À57.66
À52.0
À52.6
À69.37
À45.55
À38.23
À67.33
À44.93
À51.41
À68.46
À37.15
À47.79
—
Diclofenac
Ascorbic acid
Gatioxacin
Clotrimazole
À6.184
—
—
—
À6.288
À85.23
—
—
—
À89.15
—
—
—
À5.553
—
—
—
À56.38
—
—
—
—
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This signies that the synthesized compounds possess anti-
bacterial and antifungal activities in addition to antioxidant
and anti-inammatory activities. Docking scores along with the
binding free energies for all the synthesized compounds have
been quantied and tabulated in Table 7. The average predicted
activities of different chemical methods have been calculated
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We herein, reported the new scaffolds 6(a–d) and 8(a–l) were
synthesized by using a microwave irradiation method to ob-
tained better yield as compared to conventional heating
method. The use of a DMF : water (1 : 1) solvent system helped
in increasing the product yield through traditional, conven-
tional and microwave irradiation routes. However, we observed
greater yields via the microwave irradiation route in lesser
duration. Biological evaluations and molecular docking studies
revealed an increase in the activity of the target compounds
from their intermediates. Compounds 8d, 8e, 8h and 8k showed
excellent hydrogen bonding interactions with His-88, Val-191
and water.
´
´
19 D. Olmedo, R. Sancho, L. M. Bedoya, J. L. Lopez-Perez,
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´
E. D. Olmo, E. Munoz, J. Alcamı, M. P. Gupta and
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Conflicts of interest
21 D. Ashok, E. V. L. Madhuri and M. Sarasija, Asian J. Chem.,
2020, 32(1), 205–208.
There are no conicts to declare.
22 N. Kuntala, J. R. Telu, V. Banothu, S. B. Nallapati, J. S. Anireddy
and S. Pal, MedChemComm, 2015, 6(9), 1612–1619.
23 P. Neeraja, S. Srinivas, K. Mukkanti, P. K. Dubey and S. Pal,
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24 N. Kuntala, J. R. Telu, V. Banothu, S. Balasubramanian,
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Acknowledgements
Author Ravinder Dharavath (File No. 09/132(0865)/2017-EMR-I)
is grateful to CSIR, New Delhi, for nancial assistance in the
form of SRF. One of the authors D. Ashok is thankful to UGC-
New Delhi, for the award of BSR Faculty Fellowship. Authors
NN and MRR are thankful to UGC-New Delhi. The authors
thankful to The Head, Department of Chemistry, Osmania
University, Hyderabad, for providing laboratory facilities. We
thank CFRD, Osmania University analytical team for providing
spectral analysis facilities.
ˇ
´
25 A. M. Macan, A. Harej, I. Cazin, M. Klobucar, V. Stepanic,
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