• Deepali M. Jagdale Department of Pharmaceutical Chemistry, Bharati Vidyapeeth’s College of Pharmacy, sector 8, C. B. D. Belapur, Navi Mumbai, India, 400614
  • Ramaa C. S. Department of Pharmaceutical Chemistry, Bharati Vidyapeeth’s College of Pharmacy, sector 8, C. B. D. Belapur, Navi Mumbai, India, 400614


Objective: Malonyl CoA decarboxylase (MCD) enzyme plays important role in fatty acid and glucose oxidation. Inhibition of MCD might turn to a novel approach to treat ischemia. The main objective of this research article was to develop a novel pharmacophore for enhanced activity.

Methods: Three-dimensional quantitative structure-activity relationships (3D-QSAR) was performed for pyrazoline derivatives as MCD inhibitors using VLife MDS 4.6 software. The QSAR model was developed using the stepwise 3D-QSAR kNN-MFA method.

Results: The statistical results generated from kNN-MFA method indicated the significance and requirements for better MCD inhibitory activity. The information rendered by 3D-QSAR model may render to better understanding and designing of novel MCD inhibitors.

Conclusion: 3D-QSAR is an important tool in understanding the structural requirements for the design of novel and potent MCD inhibitors. It can be employed to design new drug discovery.

Keywords: 3D-QSAR, MCD inhibitors, kNN-MFA model, Stepwise variable selection method


Download data is not yet available.


1. Ussher JR, Lopaschuk GD. The malonyl-CoA axis as a potential target for treating ischemic heart disease. Cardiovasc Res 2008;79:259-68.
2. Stanley WC, Recchia FA, Lopaschuk GD. Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 2005;85:1093-129.
3. Frink RJ. Sudden cardiac death is not caused by ischemia. Int J Cardiovasc Res 2012;1:1-2.
4. Jaswal JS, Keung W, Wang W, Ussher JR, Lopaschuk GD. Targeting fatty acid and carbohydrate oxidation-A novel therapeutic intervention in the ischemic and failing heart. Biochim Biophys Acta 2011;1813:1333-50.
5. Fillimore N, Lopaschuk GD. Targeting mitochondrial oxidative metabolism as an approach to treat heart failure. Biochim Biophys Acta 2013;1833:857-65.
6. Dyck JRB, Cheng JF, Stanley WC, Rick B, Chandler MP, Brown S, et al. Malonyl coenzyme A decarboxylase inhibition protects the ischemic heart by inhibiting fatty acid oxidation and stimulating glucose oxidation. Circ Res 2004;94:e78-e84.
7. Bandopadhyay GK, Yu JG, Ofrecio J, Olefsky JM. Increased malonyl CoA levels in muscle from obese and type 2 diabetic subjects lead to decreased fatty acid oxidation and increased lipogenesis; Thiazolidinedione treatment reverses these defects. Diabetes 2006;55:2277-85.
8. Walters AM. Mitochondria as a drug target in ischemic heart disease and cardiomyopathy. Circ Res 2012;111:1222-36.
9. Dyck JRB, Lopaschuk GD. Malonyl-CoA control of fatty acid oxidation in the ischemic heart. J Mol Cell Cardiol 2002;34:1099-109.
10. Cheng JF, Liu B, Angeles L, Arrhenius T, Mar D, Wilson ME, et al. Cyanoguanidine based azole compounds useful as malonyl-CoA decarboxylase inhibitors. U. S. Patent 2005;7:786, 145.
11. Clifford DL, Lopaschuk GD. Role of malonyl-CoA in heart disease and the hypothalamic control of obesity. Cardiovasc Res 2007;73:278-87.
12. Abel ED. Glucose for the aging heart. Circ 2007;116:884-7.
13. Havrylyuk D, Zimenkovsky B, Vasylenko O, Zaprutko L, Gzella A, Lesky R. Synthesis of novel thiazolone based compounds containing pyrazoline moiety and evaluation of their anticancer activity. Eur J Med Chem 2009;44:1396-404.
14. Shaharyar M, Siddiqui AA, Ali MA, Sriram D, Yogeeswari P. Synthesis and in vitro antimycobacterial activity of N1-nicotinoyl-3-(4′-Hydroxy-3′-Methyl Phenyl)-5 [(sub) phenyl] 2-Pyrazolines. Bioorg Med Chem Lett 2006;16:3947–9.
15. Dipankar B, Hirakmoy C, Asish B, Abhijit C. 2-pyrazoline: a pharmacologically active moiety. Int Res J Pharm Appl Sci 2011;1:68-80.
16. Abdel-Aziz M, Gamal-Eldeen AM. Synthesis and screening of anti-cancer, antioxidant, and anti-inflammatory activities of novel galloyl pyrazoline derivatives. Pharm Biol 2009;47: 854–63.
17. Patel MR, Talele TT. 3D-QSAR studies on malonyl coenzyme A decarboxylase inhibitors. Bioorg Med Chem 2007;15:4470-80.
18. Gandhi PS, Gaikwad PL, Jagdale DM, Kadam VJ. Synthesis, characterization and antimicrobial studies of novel 2-pyrazoline derivatives containing thiazolone moiety. Int J Univ Pharm Biosci 2013;2:648-58.
19. Jagdale DM, Ramaa CS. Design, synthesis and in vitro evaluation of some small molecules malonyl CoA decarboxylase inhibitors containing pyrazoline scaffold and study of their binding interactions with malonyl CoA decarboxylase via preliminary docking simulation. Med Chem Res 2017;26:2127-40.
20. VLife Molecular Design Suite 4.6, V Life Sciences Technologies Pvt. Ltd; www.vifescience.com. [Last accessed on 20 Mar 2017]
21. Ajmani S, Jadhav K, Kulkarni S. Three dimensional QSAR using the k-Nearest Neighbour Method and its interpretation. J Chem Inf Model 2006;46:24-31.
22. Balaje R, Dhanarajan MS. 3D QSAR studies of identified compounds as potential inhibitors for anti-hyperglycemic targets. Asian J Pharm Clin Res 2014;7:362-4.
23. Shen M, LeTiran A, Xiao Y, Golbraikh A, Kohn H, Tropsha A. Quantitative structure-activity relationship analysis of functionalized amino acid anticonvulsant agents using k Nearest neighbor and simulated annealing PLS methods. J Med Chem 2002;45:2811-23.
24. Jain SV, Ghate M, Bhandoria KS, Bari SB, Chaudhary A, Borse JS. 2D, 3D-QSAR and docking studies of 1,2,3-thiadiazole thioacetamides analogues as potent HIV-1 non-nucleoside reverse transcriptase inhibitors. Org Med Chem Lett 2012;2:1-13.
25. Raji K, Muthukumar V. Quantitative structure-activity relationship analysis of the anticonvulsant activity of erythrinine. Asian J Pharm Clin Res 2016;9:125-9.
172 Views | 524 Downloads
How to Cite
Jagdale, D. M., and R. C. S. “QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS OF NOVEL PYRAZOLINE DERIVATIVES USING K NEAREST NEIGHBOUR MOLECULAR FIELD ANALYSIS METHOD”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 9, no. 12, Dec. 2017, pp. 87-91, doi:10.22159/ijpps.2017v9i12.19401.
Original Article(s)