Application of 3D-QSAR, Pharmacophore, and Molecular Docking in the Molecular Design of Diarylpyrimidine Derivatives as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors

International Journal of Molecular Sciences
Genyan LiuShuangxi Gu

Abstract

Diarylpyrimidines (DAPYs), acting as HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs), have been considered to be one of the most potent drug families in the fight against acquired immunodeficiency syndrome (AIDS). To better understand the structural requirements of HIV-1 NNRTIs, three-dimensional quantitative structure⁻activity relationship (3D-QSAR), pharmacophore, and molecular docking studies were performed on 52 DAPY analogues that were synthesized in our previous studies. The internal and external validation parameters indicated that the generated 3D-QSAR models, including comparative molecular field analysis (CoMFA, q 2 = 0.679, R 2 = 0.983, and r pred 2 = 0.884) and comparative molecular similarity indices analysis (CoMSIA, q 2 = 0.734, R 2 = 0.985, and r pred 2 = 0.891), exhibited good predictive abilities and significant statistical reliability. The docking results demonstrated that the phenyl ring at the C₄-position of the pyrimidine ring was better than the cycloalkanes for the activity, as the phenyl group was able to participate in π⁻π stacking interactions with the aromatic residues of the binding site, whereas the cycloalkanes were not. The pharmacophore model and 3D-QSAR contour maps provided...Continue Reading

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Mar 21, 2017·Bioorganic & Medicinal Chemistry Letters·Ping XueShuang-Xi Gu

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Citations

Mar 12, 2019·Current Protein & Peptide Science·Alex F M MonteiroLuciana Scotti
May 23, 2020·Drug Design, Development and Therapy·Ying-Qi FengShuang Cao
Nov 20, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yafeng TianXiulian Ju
Nov 12, 2020·Current Opinion in Pharmacology·Shuang-Xi GuLu Huang

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Software Mentioned

surflex
CoMSIA
Sybyl
GALAHAD
CoMFA
Genetic Hypermolecular Alignment of Datasets ( GALAHAD )

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