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Ashraf H Abadi

Ashraf H Abadi

German University in Cairo, Egypt

Title: Discovery of highly potent anti-HCV with new core scaffolds and new conformational aspects

Biography

Biography: Ashraf H Abadi

Abstract

NS5A is a dimeric protein and an interesting target to inhibit the replication of HCV. Reported here are two series of symmetric molecules with the scaffolds of 4, 4'-(buta-1,3-diyne- 1,4-diyl) dianiline core- and  3, 3'-(buta-1,3-diyne- 1,4-diyl) dianiline core, connected to a L/D-proline moiety, and capped with the methyl, ethyl, butyl, isobutyl and benzyl carbamate of L/D-valine, L/D-leucine and L-isoleucine amino acids. The compounds showed inhibitory effect on the replication of HCV genotype 1b in vitro with EC50s in the low picomolar range and SI50s of several orders of magnitude, Also some of the compounds showed pan-genotypic activitiy. Higher activities were associated with compounds showing curving of the core scaffolds that leads to better fit and interaction with the desired target.