Research Article | Volume: 8, Issue: 5, May, 2018

QSAR, Molecular Docking and Dynamics Studies of Quinazoline Derivatives as Inhibitor of Phosphatidylinositol 3-Kinase

Muhammad Arba Ruslin Waode Umi Kalsum Armid Alroem Muhammad Zakir Muzakkar Ida Usman Daryono Hadi Tjahjono   

Open Access   

Published:  May 30, 2018

DOI: 10.7324/JAPS.2018.8501
Abstract

Phosphatidylinositol 3-kinase (PI3K) plays a prominent role in regulating various crucial cellular functions. Many studies have indicated the involvement of PI3K in tumorigenesis. In the current study, thirty-one quinazoline derivatives were utilized to build a Quantitative Structure-Activity Relationship (QSAR) model which correlates structural feature with PI3K inhibition. The statistically robust QSAR model is pIC50 = 2.515 + 0.000005 (AM1_Eele) + 0.004 (AM1_HF) + 1.170 (AM1_LUMO) − 0.117 (apol) + 0.003 (ASA_H) with a leave-one-out cross-validation coefficient (q2) of 0.6058 and external validation (R2pred) of 0.7725. A novel compound (SC25) was proposed based on the validated QSAR model. Molecular docking of the ligand on PI3K revealed the similar binding mode of SC25 and parent compound ((S)-C5) as well as native ligand (2NQ). Molecular dynamics simulation of 40 ns confirmed the conformational stability of each SC25, (S)-C5, and 2NQ, complexed with PI3K. Prediction of affinity using MM-PBSA method revealed that SC25 has a comparable affinity with that of (S)-C5 and better than that of 2NQ.


Keyword:     Docking MM-PBSA Molecular dynamics simulation Phosphatidylinositol 3-kinase QSAR Quinazoline.


Citation:

Arba M, Ruslin, Kalsum WU, Alroem A, Muzakkar MZ, Usman I, Tjahjono DH. QSAR, Molecular Docking and Dynamics Studies of Quinazoline Derivatives as Inhibitor of Phosphatidylinositol 3-Kinase. J App Pharm Sci, 2018; 8(05): 001-009.

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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