A

Dissertation
Entitled
“Design, synthesis, molecular docking and antidiabetic
activity of novel triazole hybrids”

UNDER THE GUIDANCE OF Presented By Aditya Tomar

Dr. Premlata Kumari (I19CY038)
Associate Professor, Department of Chemistry

Sardar Vallabhbhai National Institute of Technology, Surat-395007

सरदार वल्लभभाई राष्ट्रीय प्रौद्योगिकी संस्थान, सूरत-395007
2023-2024
 Table Of Contents
 Motivation

 Abstract

 Chemistry

 Result and Discussion

 Characterization Data

 Conclusion

 References
 Motivation and answer to WHY?

In India, a lot of people have diabetes—more than 77 million adults. This makes
India the country with the second most diabetes cases in the world. Experts think
this number will grow to 134 million by 2045, creating a big health problem.

This new idea comes from the urgent need for better and easier treatments to
control blood sugar and reduce diabetes complications. Even though there are
many diabetes medicines, many people in India still have trouble managing their
blood sugar levels. This leads to serious health problems like heart disease, nerve
damage, and eye damage.
 Abstract
1.Focus: This study explores 1,2,3-triazoles for their anti-diabetic properties.
2.Objective: Design, synthesize, and evaluate novel 1,2,3-triazole hybrids for potential anti-diabetic activity.
3.Method:
1. Synthesis: Used copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) for creating triazole derivatives.
2. Molecular Docking: Employed Auto Dock Vina to predict binding affinities with porcine pancreatic alpha-
amylase isoenzyme (1OSE).
4.Key Findings:
1. Binding Affinity: Compound 8c showed a strong binding affinity of -9.8 kcal/mole.
2. Interactions: Included van der Waals forces, hydrogen bonds, and π-π stacking.
5.Efficacy:
1. In Vitro and In Vivo Assays: Confirmed anti-diabetic effects.
2. Best Compound: Compound 8c had the highest inhibitory activity with an IC50 value of 0.2951 µM.
Graphical Abstract
Chemistry
 Result and Discussion
Docking of N-(4-amino-2,3-dimethylphenyl)-2-(4-((4-phenylpiperazin-1-yl) methyl)-1H-1,2,3-
triazol-1-yl) acetamide with 1OSE

Result Protein Molecule Binding Interactions

Analysis Affinity
Software (kcal/mole)

Auto Dock 1OSE N-(4-amino-2,3- -9.8 9 van der Waals

Vina dimethylphenyl)- 1 conventional
2-(4-((4- hydrogen bond
phenylpiperazin- 1 carbon hydrogen
1-yl) methyl)-1H- bond
1,2,3-triazol-1-yl) 2 pi-sigma bonds
acetamide 1 pi-pi stacked
 Result and Discussion
Compound % Inhibition IC50(µM)
(At different concentrations in µg/mL)

Concentrations %Inhibition
50 16.74±1.32 0.320
(8a)
100 28.39±2.74
150 41.13±3.54
200 66.74±2.41
50 15.47±2.48 0.347
(8b)
100 27.41±3.16
150 42.37±1.82
200 63.78±1.18
50 17.39±1.97 0.295
(8c) 100 30.14±2.44
150 45.66±1.56

200 69.41±2.74
50 11.32±1.58 0.451
(8d) 100 23.79±1.17
150 38.14±0.36

200 55.95±2.45

50 21.59±2.37 0.185
Acarbose 100 38.67±1.55

150 67.13±2.76

200 83.31±3.61
 Characterization (1H – NMR)

1H- NMR (500 MHz, DMSO-D6): δ 7.88(d,2H, Ar-H), 7.82 (s, 1H, -NH), 7.72 (d, 2H, Ar-H), 7.34
(t, 1H, Ar-H), 6.90(m, 3H, Ar-H), 5.30 (s, 1H, C-H), 5.15 (s, 1H, C-H), 3.97(s, 2H, C-H), 3.93 (t, 2H, C-
H), 3.80 (t, 2H, C-H), 3.13 (t, 2H, C-H), 2.92 (t, 2H, C-H) ppm.
 Characterization (13C – NMR)

13 C NMR (125 MHz, DMSO- D 6): δ 179.83, 163.73, 154.62, 154.05, 142.12, 140.38, 139.91,
139.70, 139.48, 139.26, 138.89, 138.83, 138.77, 138.72, 138.29, 136.19, 135.88, 134.09,
133.15, 133.12, 133.08, 133.05, 129.54 ppm.
 Conclusion

The study successfully synthesized and evaluated novel 1,2,3-triazole hybrids for their antidiabetic properties.
Molecular docking studies using Auto Dock Vina on Porcine pancreatic alpha-amylase isoenzyme 11 (1OSE)
showed significant binding affinities. Compound 8c, with a highest binding affinity of -9.8 kcal/mole, exhibited
multiple interactions, including Van der Waals forces, hydrogen bonds, and pi interactions. Other compounds, 8a,
8b, and 8d, displayed similar interactions with notable binding affinities.

In conclusion, the novel 1,2,3-triazole hybrids synthesized in this study exhibit promising antidiabetic properties.
They have the potential to be developed into effective antidiabetic agents, targeting both enzyme inhibition and
improved insulin sensitivity.
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Thank You