Novel Benzoxazin-3-one Derivatives: Design, Synthesis, Molecular Modeling, Anti-HIV-1 and Integrase Inhibitory Assay-Reference-Cited by-同舟云学术

Novel Benzoxazin-3-one Derivatives: Design, Synthesis, Molecular Modeling, Anti-HIV-1 and Integrase Inhibitory Assay

Published:2020-11-06 Issue:7 Volume:16 Page:938-946
ISSN:1573-4064
Container-title:Medicinal Chemistry
language:en
Short-container-title:MC

Author:

Safakish Mahdieh¹,Hajimahdi Zahra¹,Vahabpour Rouhollah²,Zabihollahi Rezvan²,Zarghi Afshin¹^ORCID

Affiliation:

1. Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2. Medical Lab Technology Department, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

Introduction: Integrase is a validated drug target for anti-HIV-1 therapy. The second generation integrase inhibitors display π-stacking interaction ability with 3’-end nucleotide as a streamlined metal chelating pharmacophore. Method: In this study, we introduced benzoxazin-3-one scaffold for integrase inhibitory potential as bioisostere replacement strategy of 2-benzoxazolinone. Results: Molecular modeling studies revealed that amide functionality alongside oxadiazole heteroatoms and sulfur in the second position of oxadiazole ring could mimic the metal chelating pharmacophore. The halobenzyl ring occupies hydrophobic site created by the cytidylate nucleotide (DC-16). Conclusion: The most potent and selective compound displayed 110 μM IC50 with a selectivity index of more than 2.

Funder

Shahid Beheshti University of Medical Sciences

Publisher

Bentham Science Publishers Ltd.

Subject

Drug Discovery

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