Molecular Design, Synthesis and Cell Based HCV Replicon Assay of Novel Benzoxazole Derivatives

M. A. H. Ismail; M. Adel; N.S. M. Ismail; K.A. M. Abouzid

doi:10.1055/s-0032-1331765

Drug Research, Inhaltsverzeichnis

Drug Res (Stuttg) 2013; 63(03): 109-120
DOI: 10.1055/s-0032-1331765

Original Article

Molecular Design, Synthesis and Cell Based HCV Replicon Assay of Novel Benzoxazole Derivatives

M. A. H. Ismail

¹Pharmaceutical Chemistry Department, Faculty of Pharmacy Ain Shams University, Cairo, Egypt

,

M. Adel

¹Pharmaceutical Chemistry Department, Faculty of Pharmacy Ain Shams University, Cairo, Egypt

,

N.S. M. Ismail

¹Pharmaceutical Chemistry Department, Faculty of Pharmacy Ain Shams University, Cairo, Egypt

,

K.A. M. Abouzid

¹Pharmaceutical Chemistry Department, Faculty of Pharmacy Ain Shams University, Cairo, Egypt

› Institutsangaben

Abstract

Hepatitis C virus inhibitors based on benzoxazole scaﬀold were designed based on molecular modeling simulation study including docking into the NS5B polymerase active site. Several compounds showed significant high simulation docking scores relative to the assigned benzimidazole lead compound. The designed compounds were synthesized, structurally elucidated and their antiviral activity was evaluated through cell-based replicon in cultured Huh 5-2 cells. A number of the synthesized compounds showed significant inhibitory activity ranging from (52.2% inhibition up to 98% at<50 µg/mL). N-Benzyl-2-phenylbenzo[1,3]oxazole-5-carboxamide (8b) and N-Phenethyl-2-phenylbenzo[1,3] oxazole-5-carboxamide (8c) demonstrated genuine HCV inhibitory activity with EC₅₀ values of 41.6 and 24.5 µg/mL respectively.

Key words

molecular modeling - hepatitis C virus inhibitors - replicon assay - benzoxazole derivatives

Volltext

Referenzen

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