Research Article | Volume: 8, Issue: 10, October, 2018

Molecular modeling of 4-fluoropyrrolidine-2-carbonitrile and octahydrocyclopenta[b]pyrrole-2-carbonitrile as a dipeptidyl peptidase IV (DPP4) inhibitor

Muhammad Arba Ruslin Ruslin Nur Illiyyin Akib Yamin Yamin Sabarudin Ombe Jessi Jessi Muhammad Zakir Muzakkar Daryono Hadi Tjahjono   

Open Access   

Published:  Oct 31, 2018

DOI: 10.7324/JAPS.2018.81001

Research on the quantitative structure–activity relationship (QSAR) of the 4-fluoropyrrolidine-2-carbonitrile and octahydrocyclopenta[b]pyrrole-2-carbonitrile as dipeptidyl peptidase IV (DPP4) inhibitor was performed. The molecular descriptors were calculated and the best QSAR model was developed, which satisfied statistical parameters such as correlation coefficient R = 0.912 and leave-one-out validation coefficients q2 = 0.608. The predictive quality of the model was tested against test set compounds with R2pred value of 0.7057. A novel compound (ND1) was designed and its predicted IC50 was predicted, which was lower compared with that of the parent compound (S24). Molecular docking and molecular dynamics simulation of 40 ns showed the stability of binding orientation of ND1, the parent compound, and native ligand of DPP4. Prediction of affinity using molecular mechanics/Poisson-Boltzmann/surface area method revealed that the ND1 has a comparable affinity with the parent and natural ligands.

Keyword:     Dipeptidyl peptidase carbonitrile QSAR docking molecular dynamic simulation MM-PBSA.


Arba M, Ruslin R, Akib N, Yamin Y, Ombe S, Jessi J, et al. Molecular modeling of 4-fluoropyrrolidine-2-carbonitrile and octahydrocyclopenta[b]pyrrole-2-carbonitrile as a Dipeptidyl Peptidase IV (DPP4) Inhibitor. J App Pharm Sci, 2018; 8(10): 001-007.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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