Discovery of the 2-phenyl-4,5,6,7-Tetrahydro-1H-indole As a Novel Anti-hepatitis C Virus Targeting Scaffold

Overview

Journal Eur J Med Chem

Specialty Chemistry

Date 2015 Apr 19

PMID 25890075

Citations 6

Authors

Ivan A Andreev

Dinesh Manvar

Maria Letizia Barreca

Dmitry S Belov

Amartya Basu

Noreena L Sweeney

Nina K Ratmanova

Evgeny R Lukyanenko

Giuseppe Manfroni

Violetta Cecchetti

David N Frick

Andrea Altieri

Neerja Kaushik-Basu

Alexander V Kurkin

Affiliations

Soon will be listed here.

Abstract

Although all-oral direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) treatment is now a reality, today's HCV drugs are expensive, and more affordable drugs are still urgently needed. In this work, we report the identification of the 2-phenyl-4,5,6,7-Tetrahydro-1H-indole chemical scaffold that inhibits cellular replication of HCV genotype 1b and 2a subgenomic replicons. The anti-HCV genotype 1b and 2a profiling and effects on cell viability of a selected representative set of derivatives as well as their chemical synthesis are described herein. The most potent compound 39 displayed EC50 values of 7.9 and 2.6 μM in genotype 1b and 2a, respectively. Biochemical assays showed that derivative 39 had no effect on HCV NS5B polymerase, NS3 helicase, IRES mediated translation and selected host factors. Thus, future work will involve both the chemical optimization and target identification of 2-phenyl-4,5,6,7-Tetrahydro-1H-indoles as new anti-HCV agents.

Citing Articles

Three Component Cascade Reaction of Cyclohexanones, Aryl Amines, and Benzoylmethylene Malonates: Cooperative Enamine-Brønsted Acid Approach to Tetrahydroindoles.

Cortes Vazquez J, Alharbi W, Davis J, Moore A, Nesterov V, Cundari T ACS Omega. 2022; 7(49):45341-45346.

PMID: 36530259 PMC: 9753174. DOI: 10.1021/acsomega.2c05909.

Indole - a promising pharmacophore in recent antiviral drug discovery.

Dorababu A RSC Med Chem. 2021; 11(12):1335-1353.

PMID: 34095843 PMC: 8126882. DOI: 10.1039/d0md00288g.

Discovery of 3-Amino-2-Hydroxypropoxyisoflavone Derivatives as Potential Anti-HCV Agents.

Lee J, Lin C, Tseng C, Chen Y, Tzeng C, Tseng C Molecules. 2018; 23(11).

PMID: 30400244 PMC: 6278568. DOI: 10.3390/molecules23112863.

Crystal structure of 3-(2-nitro-phen-yl)-1-(1-phenyl-sulfonyl-1H-indol-3-yl)propan-1-one.

Umadevi M, Raju P, Yamuna R, MohanaKrishnan A, Chakkaravarthi G Acta Crystallogr E Crystallogr Commun. 2015; 71(Pt 11):o892-3.

PMID: 26594584 PMC: 4645035. DOI: 10.1107/S2056989015020162.

Crystal structure of N-{[3-bromo-1-(phenyl-sulfon-yl)-1H-indol-2-yl]meth-yl}benzene-sulfonamide.

Umadevi M, Raju P, Yamuna R, MohanaKrishnan A, Chakkaravarthi G Acta Crystallogr E Crystallogr Commun. 2015; 71(Pt 10):o756-7.

PMID: 26594460 PMC: 4647446. DOI: 10.1107/S2056989015016874.

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