Synthesis, Antiviral Activity, and Structure-Activity Relationship of 1,3-Benzodioxolyl Pyrrole-Based Entry Inhibitors Targeting the Phe43 Cavity in HIV-1 gp120.

ABSTRACT: The pathway by which HIV-1 enters host cells is a prime target for novel drug discovery because of its critical role in the life cycle of HIV-1. The HIV-1 envelope glycoprotein gp120 plays an important role in initiating virus entry by targeting the primary cell receptor CD4. We explored the substitution of bulky molecular groups in region I in the NBD class of entry inhibitors. Previous attempts at bulky substituents in that region abolished antiviral activity, even though the binding site is hydrophobic. We synthesized a series of entry inhibitors containing the 1,3-benzodioxolyl moiety or its bioisostere, 2,1,3-benzothiadiazole. The introduction of the bulkier groups was well tolerated, and despite only minor improvements in antiviral activity, the selectivity index of these compounds improved significantly.

SUBMITTER: Curreli F 

PROVIDER: S-EPMC6446940 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature