Phthalimide Derivatives with Bioactivity Against : Synthesis, Evaluation, and Computational Studies Involving Cytochrome Inhibition

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2019 Aug 29

PMID 31459076

Citations 4

Authors

Celso Yassuo Okada-Junior

Gustavo Claro Monteiro

Anna Caroline Campos Aguiar

Victor Sousa Batista

Juliana Oliveira de Souza

Guilherme Eduardo Souza

Renata Vieira Bueno

Glaucius Oliva

Nailton M Nascimento-Junior

Rafael Victorio Carvalho Guido

Vanderlan Silva Bolzani

Affiliations

Soon will be listed here.

Abstract

We describe herein the design and synthesis of -phenyl phthalimide derivatives with inhibitory activities against (sensitive and resistant strains) in the low micromolar range and noticeable selectivity indices against human cells. The best inhibitor, 4-amino-2-(4-methoxyphenyl)isoindoline-1,3-dione (), showed a slow-acting mechanism similar to that of atovaquone. Enzymatic assay indicated that inhibited cytochrome complex. Molecular docking studies suggested the binding mode of the best hit to Qo site of the cytochrome complex. Our findings suggest that is a promising candidate for hit-to-lead development.

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