Autor(es): Ching Kuan-Chieh, Kam Yiu-Wing, Merits Andres, Ng Lisa F P, Chai Christina L L

Resumo: Chikungunya virus (CHIKV) is a re-emerging vector-borne alphavirus - is transmitted to humans by Aedes mosquitoes. Despite the re-emergence of CHIKV as an epidemic threat, there is no approved effective antiviral treatment currently available for CHIKV. Herein, we report the synthesis - structure-activity relationship studies of a class of thieno[3,2-b]pyrroles - the discovery of a trisubstituted thieno[3,2-b]pyrrole 5-carboxamide 15c that exhibits potent inhibitory activity against in vitro CHIKV infection. Compound 15c displayed low micromolar activity (EC50 value of ca. 2 ?M) - limited cytotoxic liability (CC50 > 100 ?M) therefore furnishing a selectivity index of greater than 32. Notably, 15c not only controlled viral RNA production, but efficiently inhibited the expression of CHIKV nsP1, nsP3, capsid, - E2 proteins at a concentration as low as 2.5 ?M. More importantly, 15c also demonstrated broad spectrum antiviral activity against other clinically important alphaviruses such as O'nyong-nyong virus - Sindbis virus.

Imprenta: Journal of Medicinal Chemistry, v. 58, n. 23, p. 9196-9213, 2015

Identificador do Objeto Digital: 10.1021/acs.jmedchem.5b01047

Descritores: Chikungunya virus - Biochemistry ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya Virus - Virus ; Chikungunya virus - Epidemic ; Chikungunya virus - Immunology

Data de Publicação: 2015