Ankita, Keerti Bhardwaj, Navneet Khurana, Ashish Sutte, Gopal Khatik
Ankita1, Keerti Bhardwaj2, Navneet Khurana3, Ashish Sutte4, Gopal Khatik1*
1Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar- Delhi G.T. Road, Phagwara, Punjab, India (144411).
2Department of Pharmaceutics, School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar- Delhi G.T. Road, Phagwara, Punjab, India (144411).
3Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar- Delhi G.T. Road, Phagwara, Punjab, India (144411).
4Department of Pharmacognosy, School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar- Delhi G.T. Road, Phagwara, Punjab, India (144411).
Volume - 13,
Issue - 11,
Year - 2020
Diabetes is a heterogeneous disease of carbohydrates metabolism that occurs owing to a deficiency of discharge of insulin or resistance to it. Type 2 Diabetes Mellitus is very common and is a major concern. A patient over the age of 40 years mainly suffers from this and it is also increased with the increase in age and increase in obesity. Targeting to the disease progressing enzyme or protein is a valuable tool to alleviate the disease. Among several targets for diabetes, DPP-4 is recognized to control glucose metabolism. It degrades the GLP-1 or incretin which is supposed to be involved in glucagon release inhibition as well as augmented insulin secretion. Thus DPP-4 inhibitors like saxagliptin and sitagliptin are inhibiting DDP-4 leads to improve glycemic control. Therefore we have designed different novel DPP-4 inhibitors based on alogliptin which act as an antidiabetic agent with the help of Autodock vina molecular docking software. Among studies designed molecules, ANK4 showed good binding affinity (-10.7 kcal\mol) which is better than alogliptin (-9.6 kcal/mol).
Cite this article:
Ankita, Keerti Bhardwaj, Navneet Khurana, Ashish Sutte, Gopal Khatik. Identification of Dipeptidyl peptidase-4 (DPP-4) inhibitors as Potential Antidiabetic agents using Molecular docking study. Research J. Pharm. and Tech. 2020; 13(11):5257-5262. doi: 10.5958/0974-360X.2020.00919.1
1. Walker, R.; Whittlesea, C. Clinical pharmacy and therapeutics. Churchill Livingstone: Edinburg, 2007.
2. Baggio, L.; Drucker, D. Incretin hormones in the treatment of type 2 diabetes: Therapeutic applications of DPP-IV inhibitors. Medscape Diabetes Endocrinol 2006, 8, 1-5.
3. Seshadri, K.; Kirubha, M. Gliptins: A new class of oral antidiabetic agents. Indian J Pharm Sci 2009, 71, 608–614.
4. Drucker, D. J.; Nauck, M. A. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006, 368, 1696-1705.
5. Mentlein, R. Dipeptidyl-peptidase IV (CD26)-role in the inactivation of regulatory peptides. Regul Pept 1999, 85, 9-24.
6. Mentlein, R.; Gallwitz, B.; Schmidt, W. E. Dipeptidyl‐peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon‐like peptide‐1 (7–36) amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem 1993, 214, 829-835.
7. Vilsbøll, T.; Agersø, H.; Krarup, T.; Holst, J. J. Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects. J Clin Endocrinol Metab 2003, 88, 220-224.
8. Holst, J. J.; Deacon, C. F. Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes. Diabetes 1998, 47, 1663-1670.
9. Gupta, V.; Kalra, S. Choosing a gliptin. Indian J Endocrinol Metab 2011, 15, 298–308.
10. Scheen, A. J. Dipeptidylpeptidase-4 inhibitors (gliptins). Clin Pharmacokinet 2010, 49, 573-588.
11. Garber, A.; Foley, J.; Banerji, M.; Ebeling, P.; Gudbjörnsdottir, S.; Camisasca, R. P.; Couturier, A.; Baron, M. Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea. Diabetes Obes Metab 2008, 10, 1047-1056.
12. Kodimuthali, A.; Prasunamba, P. L.; Pal, M. Synthesis of a novel analogue of DPP-4 inhibitor Alogliptin: Introduction of a spirocyclic moiety on the piperidine ring. Beilstein J Org Chem 2010, 6, doi:10.3762/bjoc.6.71.
13. Lai, Z.-W.; Li, C.; Liu, J.; Kong, L.; Wen, X.; Sun, H. Discovery of highly potent DPP-4 inhibitors by hybrid compound design based on linagliptin and alogliptin. Eur J Med Chem 2014, 83, 547-560.
14. Li, N.; Wang, L.-J.; Jiang, B.; Guo, S.-J.; Li, X.-Q.; Chen, X.-C.; Luo, J.; Li, C.; Wang, Y.; Shi, D.-Y. Design, synthesis and biological evaluation of novel pyrimidinedione derivatives as DPP-4 inhibitors. Bioorg Med Chem Lett 2018, 28, 2131-2135.
15. Deng, X.; Shen, J.; Zhu, H.; Xiao, J.; Sun, R.; Xie, F.; Lam, C.; Wang, J.; Qiao, Y.; Tavallaie, M. S. Surrogating and redirection of pyrazolo [1, 5-a] pyrimidin-7 (4H)-one core, a novel class of potent and selective DPP-4 inhibitors. Bioorg Med Chem 2018, 26, 903-912.
16. Kaur, K.; Kaur, P.; Mittal, A.; Nayak, S.; Khatik, G. Design and molecular docking studies of novel antimicrobial peptides using Autodock molecular docking software. Asian J Pharm Clin Res 2017, Sept, 28-31.
17. Kaur, P.; Khatik, G. L. Identification of novel 5-styryl- 1,2,4-oxadiazole/Triazole derivatives as the potential antiandrogens. through molecular docking study. Int J Pharm Pharm Sci 2016, 8, 72-77.
18. 3g0b accessed from https://www.rcsb.org/structure/3g0b=. Accessed on 10 oct 2018.
19. Trott, O.; Olson, A. J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010, 31, 455-461.
20. Energy minimizations were performed MM2 Interface program on ChemBio3D Ultra 12.0, and structures were drawn by ChemBioDrwa Ultra 12.0 (CambridgeSoft).
21. Bashary, R. and Khatik, G.L. Design, and facile synthesis of 1, 3 diaryl-3-(arylamino) propan-1-one derivatives as the potential alpha-amylase inhibitors and antioxidants. Bioorg Chem 2018, 82, 156-162.
22. Kaur, P., Mittal, A., Nayak, S.K., Vyas, M., Mishra, V., Khatik, G.L. Current Strategies and Drug Targets in the Management of Type 2 Diabetes Mellitus. Curr Drug Targets 2018, 19(15), 1738-1766.
23. Osanyinpeju, O.S., Bashary, R., Mittal, A., Mittal, Vyas, M., Nayak, S.K., Khatik, G.L. A comparative study of stereochemical effects of anti-prostate agents by molecular docking. Asian J Pharm Clin Res 2018, 11(2), 76-80.
24. Ramjith U.S., Muhammed S. Molecular Docking Study of Novel Imidazo[2,1-b]-1,3,4 thiadiazole derivatives. Research J. Pharm. and Tech 2013, 6(6), 688-694.
25. Sravani, M., Duganath, N., Gade, D.R., Reddy R.C.H. Insilico Analysis and Docking of Imatinib Derivatives Targeting BCR-ABL Oncoprotein for Chronic Myeloid Leukemia. Asian J. Research Chem. 2012, 5(1), 153-158.
26. Chauhan, R., Singh, N., Abraham, J. Bioactivity and Molecular Docking of Secondary Metabolites produced by Streptomyces xanthochromogenes JAR5. Research J. Pharm. and Tech. 2015, 8(3), 300-309.
27. Shanmugapriya, E., Ravichandiran, V., Aanandhi, M.V. Molecular docking studies on naturally occurring selected flavones against protease enzyme of Dengue virus. Research J. Pharm. and Tech. 2016, 9(7), 929-932.
28. Dhananjayan, K., Sumathy, A., Palanisamy, S. Molecular Docking Studies and in-vitro Acetylcholinesterase Inhibition by Terpenoids and Flavonoids. Asian J. Research Chem. 2013, 6(11), 1011-1017.
29. Reddy, N.V.L.S., Anarthe S.J., Raju, G.M, Akhila, M, Raj, P.G.B.. Molecular docking studies of isolated compounds from Cassia fistula on HMG-COA reductase. Asian J. Research Chem. 2019, 12(2), 89-93.
30. Napoleon, A.A., Sharma, V. Molecular Docking and In-vitro anti-inflammatory evaluation of Novel Isochromen-1-one analogues from Etodolac. Research J. Pharm. and Tech. 2017, 10(8), 2446-2450.
31. Suganya, J., Viswanathan T., Radha, M., Marimuthu, N. In silico Molecular Docking studies to investigate interactions of natural Camptothecin molecule with diabetic enzymes. Research J. Pharm. and Tech. 2017, 10(9), 2917-2922.
32. Hemalatha, K., Girija K. Evaluation of Drug Candidature of some Benzimidazole Derivatives as Biotin Carboxylase Inhibitors: Molecular docking and Insilico studies. Asian J. Res. Pharm. Sci. 2016, 6(1), 15-20.
33. Hemalatha, K., Selvin, J., Girija, K. Synthesis, In silico Molecular Docking Study and Anti-bacterial Evaluation of some Novel 4-Anilino Quinazolines. Asian J. Pharm. Res. 2018, 8(3), 125-132.