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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.
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Contributor : Noé Ochida <>
Submitted on : Tuesday, December 22, 2020 - 11:58:49 PM
Last modification on : Friday, January 15, 2021 - 3:02:22 AM



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, Wiley-VCH Verlag, 2020, 15 (15), pp.1453-1463. ⟨10.1002/cmdc.202000124⟩. ⟨pasteur-03086888⟩



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