3D-QSAR and Molecular Docking Studies on Benzotriazoles as Antiproliferative Agents and Histone Deacetylase Inhibitors

Abstract

Benzotriazole is an important synthetic auxiliary for potential clinical applications. A series of benzotriazoles as potential antiproliferative agents by inhibiting histone deacetylase (HDAC) were recently reported. Threedimensional quantitative structure-activity relationship (3D-QSAR), including comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), were performed to elucidate the 3D structural features required for the antiproliferative activity. The results of both ligand-based CoMFA model (q 2 = 0.647, r 2 = 0.968, r 2 pred = 0.687) and CoMSIA model (q 2 = 0.685, r 2 = 0.928, r 2 pred = 0.555) demonstrated the highly statistical significance and good predictive ability. The results generated from CoMFA and CoMSIA provided important information about the structural characteristics influence inhibitory potency. In addition, docking analysis was applied to clarify the binding modes between the ligands and the receptor HDAC. The information obtained from this study could provide some instructions for the further development of potent antiproliferative agents and HDAC inhibitors.

Advances in synthesis and biological activities of benzotriazole analogues: A micro review

“…This molecular docking (MD) investigation looked into the hydrophobic interactions involving the BTZ phenyl moieties and Leu265, Phe141, Lys267, Tyr297, and Tyr196 of the enzyme binding pocket (Figure 8). A 3D quantitative SAR (3D‐QSAR) and further MD studies on this class of compounds were performed in order to acquire information for the rational design of new BTZs with enhanced anti‐proliferative activity [45].…”

“…this class of compounds were performed in order to acquire information for the rational design of new BTZs with enhanced anti-proliferative activity [45].…”

Benzotriazole: An overview on its versatile biological behavior

“…51). Three dimensional quantitative structureeactivity relationship (3D-QSAR) and additional molecular docking studies on this class of compounds were performed to obtain informations for rational design of novel benzotriazoles endowed with more potent antiproliferative activity [219].…”