Identification of [1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones as novel inhibitors of Chikungunya virus replication

Capa:Identification of [1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones as novel inhibitors of Chikungunya virus replication

Autor(es): Gigante Alba, Canela María-Dolores, Delang Leen, Priego Eva-María, Camarasa María-José, Querat Gilles, Neyts Johan, Leyssen Pieter, Pérez-Pérez María-Jesús


Resumo: Chikungunya virus (CHIKV) is a re-emerging Alphavirus that is transmitted to humans by Aedes mosquitoes. Currently, there are still no drugs or vaccines available for the treatment or prevention of this disease. Although traditionally restricted to Africa - Asia, the adaptation of the virus to Aedes albopictus, a mosquito species with an almost worldwide distribution, has contributed to the geographical spread of this virus in the past decade. Here, we report on a new family of compounds named [1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones that inhibit CHIKV replication in the low micromolar range with no toxicity to the host (Vero) cells. The most potent compound in this series has an EC50 value below 1 ?M with no cytotoxicity detected up to 668 ?M, therefore affording a selectivity index greater than 600. Interestingly, the compounds have little or no antiviral activity on the replication of other members of the Togaviridae family. The exploration - study of this class of selective inhibitors of CHIKV replication will contribute to deeper insights into the CHIKV life cycle - may be a first step toward the development of a clinical drug c-idate.


Imprenta: Journal of Medicinal Chemistry, v. 57, n. 10, p. 4000-4008, 2014


Identificador do objeto digital: 10.1021/jm401844c


Descritores: Chikungunya virus - Cell ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine


Data de publicação: 2014