M.Sc. Organic Chemistry Student Project Presentation

This presentation outline the project work carried out by the M.Sc. IV Sem organic Chemistry students, Tumkur University, Tumakuru

1. “Synthesis, Characterization, PASS prediction, In-silicoADME
and molecular docking studies of 1, 4-disubstituted-1, 2, 3-
triazole derivatives via Click approach and 1, 4, 5-
trisubstituted -1, 2, 3-triazole derivatives via Metal free
approach”
Submitted to
Department of Studies and Research in Organic Chemistry
Presentation of Project
Department of Studies and Research in Organic Chemistry
Tumkur University, Tumakuru – 572103
Under the Guidance of
Dr. Krishna Swamy G.
M.Sc., Ph.D.
Faculty
Department of Studies and Research in Organic Chemistry
Tumkur University, Tumakuru ̶ 572103
By
Ms. Kavya. R
(18POC012)
Ms. Preritha. H.J
(18POC021)
Ms. Rajeshwari. B. S
(18POC022)
Mr. Ravi Kumar. M
(18POC023)
Ms. Roopa. B
(18POC024)
Ms. Salma Banu
(18POC025)
II M.Sc. IV Semester
1

2. 1INTRODUCTION 1MATERIALS AND METHODS 1EXPERIMENTAL 1
RESULTS AND DISCUSSION
CONTENTS
1
RESULTS AND DISCUSSION
1CONCLUSION 1PUBLICATIONS 1REFERENCES 1ACKNOWLEDGEMENT
2

3. Heterocyclic chemistry is the most important and well studied branc h in medicinal
chemistry because of their bioactivity mainly due to constituent heteroato ms like
nitrogen [1, 2], sulphur [3-6], oxygen [7-8] and others [9].
INTRODUCTION
Triazoles are heterocyclic organic compound containing five membered rin g
systems
with
three
nitrogen
and
two
carbon
atoms
.
Two
isomeric
forms
of
triazoles
are
3
systems
with
three
nitrogen
and
two
carbon
atoms
.
Two
isomeric
forms
of
triazoles
are
existed namely 1, 2, 3-triazole and 1, 2, 4-triazole.
N
N
H
N
N
N
H
N
1, 2, 3-triazole1, 2, 4-triazole

4. Biological Importance of 1, 2, 3-traizoles
N
Antimicrobial agents
Antiviral agents
Anti-inflammatory agents
"Click" Reaction
NH
4
OAc, AcOH
N
N
N
R
R
1
R N
3
R
1
R
2
R
1
& R
2
= -H, EWG, EDG, Aryl & Other R = Aryl, Alkyl & Other
MeCN, rt
A
C B
Synthetic Utility of 1, 2, 3-traizoles
4
N
N
N
R
1
R
R
2
Anticancer agents
Antitubercular agents
Antiparasitic agents
Ar
O
R
1
R
2
NaN
3
MeNO
2
DMF, 100
o
C
R
TsN
3
N
R
NaN
3
Br
Xantphos
Dioxane, 90
o
C
D

5. Based on the recent reports on the pharmacological significance of 1, 2, 3-
triazoles, a project was undertaken to
Objectives of present study
R
R
1
O
NN
N
R
2
N
N
N
R
2
P
A
S
S
Characterization
Click
Approach
5
N
N
N
R
N
NO
N
R
N
NOH
P
A
S
S
ADMETox
Molecular
Docking
Metal Free
Approach

6. MATERIALS AND METHODS
Chemical and ReagentsSigma Aldrich, SD fine and Spectro chem used
without further purification.
Reaction progress and PurityChecked byTLC using Merck silica gel 60 F
254
precoated on aluminium backed plates. Spots on the
TLC plates were visualized with ultraviolet light.
Melting pointDetermined for solid compounds in Stuart Scientific
Apparatus SMP3 (UK) in open capillary tubes and
are uncorrected.
Reaction Conditions
Room
temperature
reactions
mentioned
ranges
6
Reaction Conditions
Room
temperature
reactions
mentioned
ranges
between 15-35°C. For low temperatures reactions an
ice-bath with sodium chloride (0 °C) was used.
Infrared spectrarecorded in KBr pellets onShimadzu ATR
Spectrometer. Wave numbers are expressed in cm
-1
NMR Spectra
1
H &
13
C NMR Spectra were recorded onAgilent
(400 MHz,
1
H NMR) and (100 MHz,
13
C NMR)
spectrometers using deuteriated solvents (CDCl
3or
DMSO-d
6) and Tetramethylsilane (TMS) as an
internal standard.Chemical shifts are expressed in δ
values [ppm].

7. Scheme-1: Synthetic route for the preparation of su bstituted Propynyloxy benzene and
benzaldehyde derivatives [1a-c]
R
OHR
1
R
OR
1
(i)
R = -Cl, -Br, -NO
2
R
1
= -H, -CHO
[1a-c]
Reagents and Condition:
(i) Propargyl bromide,
K
2
CO
3
, DMF, rt, 12-18 hr.
EXPERIMENTAL
A = 4-chlorophenol
B= Product
Solvent system:
Pet. Ether:Ethyl acetate (7:3)
B A
7
Scheme-2: Synthetic route for the preparation of su bstituted aromatic azide derivatives [2a-d]
(i)
R = 4-NO
2
, 3-NO
2
,
4-COCH
3
, 4-SO
2
NH
2
[2a-d]
R
NH
2
R
N
N
+
N
–
Reagents and Condition:
(i) NaNO
2
, HCl, NaN
3
, 0
o
C-
rt, 1 hr.
A = 4-nitroaniline
B= 1-azido-4-nitro benzene
Solvent system:
Pet. Ether:Ethyl acetate (7:3)
A B

8. Scheme-3: Synthetic route for the preparation of 1, 4-substituted-1, 2, 3-triazole derivatives
[3a-i] via Click approach
(i)
R = -Cl, -Br, -NO
2
R
1
= -H, -CHO
R
2
= 4-NO
2
, 3-NO
2
, 4-COCH
3
R
R
1
O
[2a-c]
R
2
N
3
[1a-c]
R
R
1
O
[3a-i]
NN
N
R
2
Reagents and Condition:
(i) CuSO
4
.5H
2
O, Sodium
Ascorbate, H
2
O-THF, rt,
12-18 hr.
A B C
A = Azide
B= Alkyne
C= Product
Solvent system: Pet.
Ether:Ethyl
acetate (7:
3)
8
Scheme-4: Synthetic route for the preparation of 1, 4-substituted-1, 2, 3-triazole
derivatives [4a-c] via Click approach
(i)
R = 4-NO
2
, 3-NO
2
, 4-COCH
3
[2a-c]
R
N
3
[4a-c]
NN
N
R
2
Reagents and Condition:
(i)CuSO
4
.5H
2
O, Sodium Ascorbate,
H
2
O-THF, rt, 12-18 hr.
Pet.
Ether:Ethyl
acetate (7:
3)
A = Azide
B= Product [4b]
Solvent system:
Pet. Ether:Ethyl acetate (7:3)
A B

9. Scheme-5:
Synthetic route for the
preparation of 1, 4, 5-
substituted-1, 2, 3-
triazole derivatives [6a-
f] via Metal free
approach
N
N
N
O
N
3
(i)
(ii)
[2a-e]
R
R = 4-NO
2
, 3-NO
2
, 4-SO
2
NH
2

4-Br, 4-COCH
3
N
N
N
O
N
N
N
O
O
O
N
N
N
O
O
9
N
N
N
[5b-d]
R
N
N
N
[5a]
N
[5f]
(iii)
NO
2
NH
2
N
N
N
HO
[6b-d]
R
N
N
N
HO
[6f]
NH
2
N
N
N
[5e]
O
N
N
N
HO
OH
N
N
N
HO
NO
2
[6a][6e]
(iii) (iii)(iii)
R = 3-NO
2
, 4-SO
2
NH
2
, 4-Br
Reagents and Condition:
(i) Et
3
N, DMF, rt, 24 hr; (ii)
Zn, AcOH-H
2
O, rt, 2 hr;
(iii) NaBH
4
, EtOH, rt, 2 hr.
A B
A = Compound [5c]
B= Product
Solvent system:
Pet. Ether:Ethyl acetate (7:3)

10. RESULTS AND DISCUSSION
The key intermediates aromatic azides were obtained from co rresponding substituted aromatic
primary amines as shown inScheme-2and terminal alkyne were prepared as depicted in Scheme-1.
Finally, 1, 4-disubstituted-1, 2, 3-triazoles were synthe sized via Click approach depicted in Scheme-
3 & 4whereas 1, 4, 5-trisubstitued-1, 2, 3-triazole were synthe sized via Metal free approach as
shown inScheme-5
.
The
assigned
structures
of
the
intermediates
and
triazole
derivatives
were
confirmed
by
10
The
assigned
structures
of
the
intermediates
and
triazole
derivatives
were
confirmed
by
their physicochemical as tabulated in table-1and spectral studies (IR, multi nuclear NMR (
1
H &
13
C) and Mass analysis).
Finally synthesized compounds subjected toin silicoPASS, ADMET and molecular
docking studies.

11. Code Molecular Formula
Molecular
Weight
Physical state M.P.(
o
C)
Yield(%)
1aC
9H
7ClO 166.6 Dark brown oil-95
1bC
10H
7BrO
2239.07 Yellow solid 93-9590
1cC
10H
7NO
4205.17 Yellow solid 90-9290
2aC
6H
6N
4O
2164.12 Yellow solid 146-148 98
2bC
6H
6N
4O
2164.12 Brown solid 118-120 97
2cC
8H
7N
3O 161.16 Orange solid 100-102 98
2dC
6H
6N
4O
2S 198.20 Pale Yellow solid 119-120 96
3aC
15H
11ClN
4O
3330.73 Brown solid 130-132 85
3bC
15H
11ClN
4O
3330.73 Light brown solid 225-228 88
3cC
17H
14ClN
3O
2327.76 Brown solid 195-197 90
3dC
16H
11BrN
4O
4403.19 Light brown solid 253-255 45
3eC
16H
11BrN
4O
4403.19 Brown solid 243-245 40
3fC
18H
14BrN
3O
3400.23 Light brown solid 235-237 50
3g
C
16
H
11
N
5
O
6
369.29
Brown solid
242
-
244
40
Table-1: Physical Characterization data of synthesi zed compounds
11
3g
C
16
H
11
N
5
O
6
369.29
Brown solid
242
-
244
40
3hC
16H
11N
5O
6369.29 Brown solid 253-255 45
3iC
18H
14N
4O
5366.33 Yellow solid 255-257 40
4aC
14H
10N
4O
2266.25 Yellow solid 244-246 55
4bC
14H
10N
4O
2266.25 Cream solid 240-242 60
4cC
16H
13N
3O 263.29 Brown solid 152-154 75
5aC
11H
10N
4O
3246.22 White solid 169-171 97
5bC
11H
10N
4O
3246.22 Pale brown solid 125-127 95
5cC
11H
12N
4O
3S 280.30 White solid 253-255 98
5dC
11H
10BrN
3O 279.00 White solid 220-222 85
5eC
13H
13N
3O
2243.26 Cream solid 159-161 98
5fC
11H
12N
4O 216.24 Brown solid 191-193 85
6aC
11H
12N
4O
3248.24 Yellow solid 253-255 90
6bC
11H
12N
4O
3248.24 Cream solid 87-89 92
6cC
11H
14N
4O
3S 282.32 White solid 250-252 90
6dC
11H
12BrN
3O 282.14 White solid 195-197 85
6eC
13H
17N
3O
2247.29 White solid 143-145 95
6fC
11H
14N
4O 218.26 Brown solid 180-182 85

12. O
2
N
O
C
C
C
H
O
H
H
H
δ

=
10.29 ppm (1H, s)
δ

=
7.51-7.49 ppm (1H, d)
δ

=
8.53-8.50 ppm (1H, dd)
δ

=
188.12 ppm
δ

=
80.42 ppm
δ

=
78.10 ppm
Spectral Interpretation
12
C
C
H
H
H
δ
=
3.75-3.74 ppm (1H, t)
δ
=
5.16-5.15 ppm (2H, d)
δ

=
8.42-8.41 ppm (1H, d)
δ
=
57.92 ppm
Figure-1: Selected
1
H and
13
C NMR
chemical shift values of compound 5-
Nitro-2-(prop-2-ynyloxy) benzaldehyde
[1c]
Figure-2:
1
H &
13
CNMR spectra of 5-Nitro-2-(prop-2-ynyloxy) benzaldehyde [1c] in
DMSO-d
6

13. Cl O
C
NN
N
H H
H
H
H
H
H
δ

=
7.34-7.33 ppm (2H, d)
δ

=
7.10-7.07 ppm (2H, d)
δ
=
5.24 ppm (2H, s)
δ

=
9.06 ppm (1H, s)
δ
=
8
.
0
7
-
8
.0
5
p
p
m

(
2
H
, d
)
δ

=
61.91 ppm
δ
=
27.42 ppm
Spectral Interpretation
13
C
O
C
H
H
H
H
H
δ
=
2.48 ppm (3H, s)
δ
=
8
.
0
7
-
8
.0
5
p
p
m

(
2
H
, d
)
δ
=
8.15-8.13 ppm (2H, d)
δ
=
197.49 ppm
Figure-3: Selected
1
H and
13
C NMR chemical shift
values of compound 1-(4-(4-((4-chlorophenoxy)
methyl)-1H-1, 2, 3-triazol-1-yl) phenyl) ethanone [3c]
Figure-4:
1
H &
13
CNMR spectra of 1-(4-(4-((4-chlorophenoxy) methyl)-1H-1, 2, 3-
triazol-1-yl) phenyl) ethanone [3c] in DMSO-d
6

14. NO
2
N
N
N
C
O
C
H
H
H
H H
H H
δ

=
8.49-8.47 ppm (2H, d)
δ
=
7.99-7.97 ppm (2H, d)
δ

=
2.50 ppm (3H, s)
δ
=
1
9
3
.
2
4

p
p
m
δ
=
9
.7
7
p
p
m
Spectral Interpretation
14
C
C
O
H
H
H
δ

=
2.65 ppm (3H, s)
δ
=
1
9
3
.
2
4

p
p
m
δ
=
27.68 ppm
δ
=
9
.7
7
p
p
m
Figure-5: Selected
1
H and
13
C NMR
chemical shift values of compound 1-(5-
methyl-1-(4-nitrophenyl)-1H-1,2,3-
triazol-4-yl) ethanone [5a]
Figure-6:
1
H &
13
CNMR spectra of 1-(5-methyl-1-(4-nitrophenyl)-1H-1,2,3-triazol-4-
yl) ethanone [5a] in DMSO-d
6

15. N
N
N
C
C
C
S
O
O
N
H H
H
H
H
H
H
H
δ

=
7.54 ppm (2H, s) δ

=
8.02-8.00 ppm (2H, d)
δ

=
7.81-7.79 ppm (2H, d)
δ

=
2.36 ppm (3H, s)
δ

=
61.21 ppm
δ

=
23.02 ppm
Spectral Interpretation
15
C OH
C
H
H
H
δ

=
4.93-4.90 ppm (1H, q/t)
δ

=
5.20-5.19 ppm (1H, d)
δ

=
1.50-1.45 ppm (3H, d)
δ

=
8.72 ppm
Figure-7: Selected
1
H and
13
C NMR chemical shift
values of compound 4-(4-(1-hydroxyethyl)-5-methyl-
1H-1, 2, 3-triazol-1-yl) benzene sulfonamide [6c]
Figure-8:
1
H &
13
CNMR spectra of 4-(4-(1-hydroxyethyl)-5-methyl-1H-1, 2, 3-triazol-
1-yl) benzene sulfonamide [6c] in DMSO-d
6

16. Prediction of Activity Spectra for Substances (PASS) (http://www.w ay2drug.com/) is software for the creation of SAR models based
on MNA descriptors and modified Bayesian algorithm. PASS approach can b e applied to so called “drug-like”substances.
PASS Analysis
These predictive results showed that all the compounds were more poten t as antimycobacterial than anti-inflammatory compared to
antibacterial as well as antifungal agents as tabulated in table-2
Code
Biological Activity
Antibacterial Antifungal Anti-inflammatory
Antimycobacterial
Pa Pi Pa Pi Pa Pi
Pa
Pi
3a0.257 0.079 0.236 0.114 0.501 0.056
0.722
0.005
3b0.240 0.089 0.210 0.131 0.473 0.065
0.729
0.005
3c0.219 0.102 0.235 0.115 0.610 0.029
0.658
0.007
3d0.317 0.054 0.356 0.061 - -
0.820
0.004
3e0.299 0.060 0.328 0.070 - -
0.824
0.003
3f0.281 0.067 0.359 0.060 0.332 0.135
0.777
0.004
3g
0.326
0.051
0.303
0.080
0.342
0.127
0.758
0.004
16
3g
0.326
0.051
0.303
0.080
0.342
0.127
0.758
0.004
3h0.310 0.056 0.278 0.091 0.324 0.140
0.763
0.004
3i0.328 0.050 0.329 0.070 0.382 0.105
0.787
0.004
4a0.232 0.094 - - 0.416 0.087
0.595
0.010
4b0.229 0.096 - - 0.393 0.099
0.607
0.010
4c0.204 0.113 - - 0.586 0.035
0.512
0.017
5a0.217 0.103 0.177 0.154 0.282 0.179
0.447
0.028
5b0.203 0.114 - - 0.262 0.200
0.454
0.027
5c- - - - 0.425 0.083
0.264
0.107
5d0.171 0.145 0.172 0.158 0.255 0.207
0.408
0.037
5e0.178 0.138 - - - -
0.344
0.057
5f0.232 0.094 - - 0.343 0.127
0.425
0.033
6a0.312 0.056 0.261 0.100 0.254 0.207
0.379
0.045
6b0.295 0.062 0.235 0.115 0.238 0.227
0.387
0.042
6c0.219 0.102 - - 0.393 0.099
0.215
0.155
6d0.254 0.081 0.256 0.103 - -
0.343
0.058
6e0.245 0.086 0.197 0.138 0.350 0.122
0.259
0.110
6f0.326 0.051 0.226 0.121 0.310 0.151
0.358
0.052
Pa-Probable to be active;
Pi-Probable to be inactive

17. ADMETox evaluation
Code
Drug likeness
LipinskiGhose Veber
Bioactivity
Score MW ≤ 500 MlogP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5
160 ≤ MW ≤
480
20 ≤ atoms ≤ 70
Rotatable bonds ≤
10
TPSA ≤ 140
3a330.73 2.07 5 0 330.73 23 5 85.760.55
3b330.73 2.07 5 0 330.73 23 5 85.76 0.55
3c327.76 2.60 4 0 327.76 23 5 57.01 0.55
3d403.19 1.57 6 0 403.19 25 6 102.830.55
3e403.19 1.57 6 0 403.19 25 6 102.830.55
3f
400.23
2.07
5
0
400.23
25
6
74.08
0.55
Table-3: Drug likeness and bioactivity score of compounds
The drug-likeness scores were calculated by considering (miLogP, TP SA, nAtoms, nON, nOHNH, rotb & MW) based on Lipinski’s,
Ghose and Veber rule for the prediction of bioactivity score were carrie d out. The results of these prediction showed that the
compounds obeyed Lipinski’s, Ghose and Veber rule except compound (3g) & (3h)which violates Veber rule ( table-3).
17
3f
400.23
2.07
5
0
400.23
25
6
74.08
0.55
3g369.29 0.92 8 0 369.29 27
7 148.65
0.55
3h369.29 0.92 8 0 369.29 27
7 148.65
0.55
3i366.33 0.57 7 0 366.33 27 7 119.90 0.55
4a266.25 2.64 4 0 266.25 20 3 76.53 0.55
4b266.25 2.64 4 0 266.25 20 3 76.53 0.55
4c263.29 2.42 3 0 263.29 20 3 47.780.55
5a246.22 0.36 5 0 246.22 18 3 93.600.55
5b246.22 0.36 5 0 246.22 18 3 93.60 0.55
5c280.30 -0.19 6 1 280.30 19 3 116.32 0.55
5d280.12 2.01 3 0 280.12 16 2 47.780.55
5e243.26 0.97 4 0 243.26 18 3 64.850.55
5f216.24 0.76 3 1 216.24 16 2 73.80 0.55
6a248.24 0.44 5 1 248.24 18 3 96.760.55
6b248.24 0.44 5 1 248.24 18 3 96.760.55
6c282.32 -0.12 6 2 282.32 19 3 119.480.55
6d282.14 2.09 3 1 282.14 16 2 50.94 0.55
6e247.29 1.13 4 2 247.29 18 3 71.17 0.55
6f218.26 0.84 3 2 218.26 16 2 76.960.55

18. CodeGI absorption BBB permeant
Log Kp
(cm/s)
3aHigh No -5.97
3bHigh No -5.97
3cHigh Yes -6.06
3dHigh No -6.75
3eHigh No -6.75
3fHigh Yes -6.83
3gLow No -7.15
3h
Low
No
-
7.15
The Brain Or IntestinaL EstimateD permeation method (BOILED-Egg) i s proposed as an accurate predictive model that works by
computing the lipophilicity and polarity of small molecules. The whit e region indicates passive gastrointestinal absorption and yellow
region indicates passive brain permeation. The derivatives BOILE D Egg image are shown infigure-9and predictions are as tabulated
intable-4.
Table-4: Predicted distribution parameters in ADME of comp ounds
18
3h
Low
No
-
7.15
3iHigh No -7.24
4aHigh Yes -5.91
4bHigh Yes -5.91
4cHigh Yes -6.00
5aHigh No -6.67
5bHigh No -6.67
5cHigh No -7.78
5dHigh Yes -6.26
5eHigh Yes -6.75
5fHigh No -6.85
6aHigh No -7.01
6bHigh No -7.01
6cHigh No -8.12
6dHigh Yes -6.61
6eHigh No -7.23
6fHigh No -7.19
Figure-9: BOILED Egg image of (5a-f) & (6a-f) derivative

19. The synthesized compounds were subjected to an in silico toxicity eva luation using Pro-Tox. The LD50 is defined as the median lethal dose of a
compound at which the test subjects die upon exposure to it. The toxicity clas s ranges from 1 to 6 as shown below
Class I: fatal if swallowed (LD50 ≤ 5)
Class II: fatal if swallowed (5 < LD50 ≤ 50)
Class III: toxic if swallowed (50 < LD50 ≤ 300)
Class IV: harmful if swallowed (300 < LD50 ≤ 2000)
Class V: may be harmful if swallowed (2000 < LD50 ≤ 5000)
Class VI: non-toxic (LD50 > 5000)
The results showed that the synthesized compounds were predicted to be harmful
if swallowed and belongs to class 4 (table-5).
Code
Predicted
LD
50
(mg/kg)
Toxicity Class
3a494 4
3b494 4
3c400 4
3d494 4
3e494 4
3f1000 4
Table-5: Predicted LD
50
and Toxicity class of the compounds
19
3g494 4
3h494 4
3i400 4
4a400 4
4b400 4
4c400 4
5a500 4
5b500 4
5c500 4
5d500 4
5e500 4
5f500 4
6a500 4
6b500 4
6c500 4
6d500 4
6e400 4
6f500 4

20. Molecular docking studies
In-silicomolecular docking is a computational technique plays important role in the rat ional design of drugs and widely used to predict
the binding orientation of small molecule drug candidates to protein ta rgets in order to predict the affinity and activity of the small
molecule.
Based on the PASS prediction crystal structure of Mycobacterium
tuberculosis enoylreductase (INHA) complexed with N-(3-chloro-2-
methylphenyl)-1-cyclohexyl- 5-oxopyrrolidine-3-carboxamide (PDB
ID: 4TZT) was downloaded from the free protein database
www.rcsb.org
. The site in which co-crystallized ligand complexed
was identified and the active pocket consisted of 27 amino acid
residues
GLY
14
,
ILE
15
,
ILE
16
,
SER
20
,
ILE
21
,
PHE
41
,
LEU
63
,
Protein preparation:
Auto dock Vina was used for docking purpose and docking results
were tabulated intable-5and all docked compounds shown in
figure-11.
20
residues
GLY
14
,
ILE
15
,
ILE
16
,
SER
20
,
ILE
21
,
PHE
41
,
LEU
63
,
ASP64, VAL65, SER94, ILE95, GLY96, MET103, ILE122,
MET147, ASP148, PHE149, PRO15, ALA157, TYR158, LYS165,
GLY192, PRO193, ILE194, THR196, MET199 and ILE215 were
selected. The grid was centered at the region surrounding important
amino acid residues as shown in Figure-10.
The ligands were drawn on Chem Draw Ultra 8.0, assigned with
proper 2D orientation and were converted to energy minimized
3D structures using Chem3D Ultra 8.0 and Gasteiger charges,
nonpolar hydrogen atoms and the rotatable bonds were set by
using AutoDock 4.2 tools.
Ligand preparation:
Figure-10: Grid box centered at the active site of 4TZT protein

21. Code
Docking energies
(Kcal/mol)
Antimycobacterial
PDB: 4ZTZ
3a-8.6
3b-8.6
3c-8.7
3d-8.5
3e-7.8
3f-7.7
3g-8.3
3h-8.5 3i-8.3
Table-5: Molecular docking results of compounds
Most active compounds were from the series(3a-i),among them compound
[3c]was most active exhibited pi-sigma interaction with ILE21 and MET 199,
Figure-11: All docked compounds in the active site of 4TZT protein
21
4a-6.3
4b-6.5
4c-6.7
5a-7.3
5b-7.2
5c-6.9
5d-7.2
5e-7.8
5f-7.0
6a-7.5
6b-7.4
6c-7.0
6d-7.0
6e-7.8
6f-6.8
pi-pi stacking with ILE21, PRO193, ILE215 & LEU218 along with alky and
pi-alky interactions as shown in figure-12.
Figure-12: Binding modes of [3c] into the active site of 4TZT protein

22. CONCLUSION
The objective of the project has been successfully complete d
2Prepared diazonium ionsin situ 2Prepared thermally stable organic azides and characterize d. 2Prepared O-propargylated derivatives and characterized v ia physicochemical and spectral means. 2Synthesized 1, 4-disubstituted-1, 2, 3-triazoles via Clic k approach and 1, 4, 5-trisubstitued-1, 2, 3-triazole
via Metal free approach
2Characterization of the synthesized molecules by physicoc hemical as well as spectroscopy means and
representative spectra has been given.
2
PASS
prediction
for
biological
activity
were
carried
out
and
identified
the
synthesized
compounds
as
2
PASS
prediction
for
biological
activity
were
carried
out
and
identified
the
synthesized
compounds
as
antimycobacterial agents.
2Finally,in silicostudies like ADMETox was carried out with conclusion that al l the synthesized molecules
acts as “drug like” with low toxicity and further molecular d ocking studies were carried out on anti-
tubercular target protein PDB ID: 4TZT and correlated with P ASS prediction.
22

23. PUBLICATIONS
23

24. 1. S. Ahmad, O. Alam, M. J. Naim, M. Shaquiquzzaman, M. M. Alam and M. Iqbal ,Eur. J. Med. Chem.,157, 527–561 (2018);
https://doi.org/10.1016/j.ejmech.2018.08.002
2. W. B. Parker,Chem. Rev.,109, 2880–2893 (2009);
https://doi.org/10.1021/cr900028p
3. K. Bozorov, L. F. Nie, J. Zhao and H. A. Aisa,Eur. J. Med. Chem.,140, 465–493 (2017);
https://doi.org/10.1016/j.ejmech.2017.09.039
4. K. Bozorov, J. Y. Zhao, B. Elmuradov, A. Pataer and H. A. Aisa,Eur. J. Med. Chem.,102, 552–573 (2015);
https://doi.org/10.1016/j.ejmech.2015.08.018
5. K. Bozorov, H. R. Ma and J. Y. Zhao,Eur. J. Med. Chem.,84, 739–745 (2014);
https://doi.org/10.1016/j.ejmech.2014.07.065
6. K. Bozorov, J. Y. Zhao and L. F. Nie, RSC Adv.,7, 31417–31427 2017;
https://doi.org/10.1039/c7ra04808d
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25. ACKNOWLEDGEMENT
Dr. S. Sreenivasa
Associate Professor,
Department of Studies and Research in Organic Chemistry
Tumkur University, Tumakuru
and
Deputy Adviser, NAAC, Bengaluru.
Dr. Krishna Swamy G
Faculty and Project Guide,
Department of Studies and Research in Organic Chemistry, Tumkur University, Tumakuru.
Dr. Aruna Kumar D B
Assistant Professor and Coordinator
Department of Studies and Research in Organic Chemistry
Tumkur University, Tumakuru.
We express deep depth of gratitude to
25
Our parents and dear friends who had been a
constant source of inspiration and moral support
throughout our work.
Tumkur University, Tumakuru.
We are also thankful to
All teaching and non-teaching
staff of our department
Tumkur University for providing the
laboratory facilities in carrying out and
successfully completing the work.

26. 26