5-Carba-pterocarpens: A new scaffold with anti-HCV activity

Talita de A Fernandes; Dinesh Manvar; Jorge L O Domingos; Amartya Basu; Daniel Brian Nichols; Neerja Kaushik-Basu; Paulo R R Costa

doi:10.1016/j.ejmech.2016.02.010

5-Carba-pterocarpens: A new scaffold with anti-HCV activity

Eur J Med Chem. 2016 Apr 13:112:33-38. doi: 10.1016/j.ejmech.2016.02.010. Epub 2016 Feb 6.

Authors

Talita de A Fernandes¹, Dinesh Manvar², Jorge L O Domingos³, Amartya Basu², Daniel Brian Nichols⁴, Neerja Kaushik-Basu⁵, Paulo R R Costa⁶

Affiliations

¹ Laboratório de Química Bioorgânica, Instituto de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco H, Ilha da Cidade Universitária, 21941-590 Rio de Janeiro, RJ, Brazil.
² Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers-The State University of New Jersey, 185 South Orange Avenue, New Jersey 07103, USA.
³ Departamento de Química Orgânica, Centro de Tecnologia e Ciências, Universidade do Estado do Rio de Janeiro, Rua São Francisco Xavier 524, Pav. Haroldo Lisboa da Cunha - s 406 - Maracanã, 20550-900 Rio de Janeiro, RJ, Brazil.
⁴ Department of Biological Sciences, Seton Hall University, 400 South Orange Avenue, New Jersey, 07079, USA.
⁵ Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers-The State University of New Jersey, 185 South Orange Avenue, New Jersey 07103, USA. Electronic address: kaushikbasu.neerja@gmail.com.
⁶ Laboratório de Química Bioorgânica, Instituto de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco H, Ilha da Cidade Universitária, 21941-590 Rio de Janeiro, RJ, Brazil. Electronic address: prrcosta2011@gmail.com.

PMID: 26874742
DOI: 10.1016/j.ejmech.2016.02.010

Abstract

The synthesis of a series of 5-carba-pterocarpens derivatives involving the cyclization of α-aryl-α-tetralones is described. Several compounds demonstrated potent activity and selectivity in vitro against HCV replicon reporter cells. The best profile in Huh7/Rep-Feo1b replicon reporter cells was observed with 2h (EC50 = 5.5 μM/SI = 20), while 2e was the most active in Huh7.5-FGR-JC1-Rluc2A replicon reporter cells (EC50 = 1.5 μM/SI = 70). Hydroxy groups at A- and D-rings are essential for anti-HCV activity, and substitutions in the A-ring at positions 3 and 4 resulted in enhanced activity of the compounds.

Keywords: BBr(3) mediated demethylation-cyclization; Carba-pterocarpens; Hepatitis C virus inhibitors; Microwave irradiation; Palladium catalyzed arylation.

Published by Elsevier Masson SAS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anisoles / chemical synthesis
Anisoles / chemistry
Anisoles / pharmacology
Antiviral Agents / chemical synthesis
Antiviral Agents / chemistry*
Antiviral Agents / pharmacology*
Catalysis
Cell Line
Guanidines / chemical synthesis
Guanidines / chemistry*
Guanidines / pharmacology*
Hepacivirus / drug effects*
Hepacivirus / genetics
Hepatitis C / drug therapy
Hepatitis C / virology
Humans
Palladium / chemistry
Replicon / drug effects
Tetralones / chemical synthesis
Tetralones / chemistry
Tetralones / pharmacology

Substances

Anisoles
Antiviral Agents
Guanidines
Tetralones
dodine
Palladium