Skip to Main content Skip to Navigation
New interface
Journal articles

Benzimidazole Derivatives as Novel Zika Virus Inhibitors

Abstract : We have synthesized 50 benzimidazole (BMZ) derivatives with 1,2-phenylenediamines and aromatic aldehydes under mild oxidation conditions by using inexpensive, nontoxic inorganic salt sodium metabisulfite in a one-pot condensation reaction and screened their ability to interfere with Zika virus (ZIKV) infection utilizing a cell-based phenotypic assay. Seven BMZs inhibited an African ZIKV strain with a selectivity index (SI=CC50 /EC50 ) of 9-37. Structure-activity relationship analysis demonstrated that substitution at the C-2, N-1, and C-5 positions of the BMZ ring were important for anti-ZIKV activity. The hybrid structure of BMZ and naphthalene rings was a structural feature responsible for the high anti-ZIKV activity. Importantly, BMZs inhibited ZIKV in human neural stem cells, a physiologically relevant system considering the severe congenital anomalies, like microcephaly, caused by ZIKV infection. Compound 39 displayed the highest antiviral efficacy against the African ZIKV strain in Huh-7 (SI>37) and neural stem cells (SI=12). Compound 35 possessed the highest activity in Vero cells (SI=115). Together, our data indicate that BMZs derivatives have to be considered for the development of ZIKV therapeutic interventions.
Complete list of metadata

https://hal-riip.archives-ouvertes.fr/pasteur-03086888
Contributor : Noé OCHIDA Connect in order to contact the contributor
Submitted on : Tuesday, December 22, 2020 - 11:58:49 PM
Last modification on : Friday, January 15, 2021 - 3:02:22 AM

Identifiers

Citation

Bui Thi Buu Hue, Phuong Hong Nguyen, Tran Quang De, Mai van Hieu, Eunji Jo, et al.. Benzimidazole Derivatives as Novel Zika Virus Inhibitors. ChemMedChem, 2020, 15 (15), pp.1453-1463. ⟨10.1002/cmdc.202000124⟩. ⟨pasteur-03086888⟩

Share

Metrics

Record views

11