Ligand design, synthesis and biological anti-HCV evaluations for genotypes 1b and 4a of certain 4-(3- & 4-[3-(3,5-dibromo-4-hydroxyphenyl)-propylamino] phenyl) butyric acids and 3-(3,5-dibromo-4-hydroxyphenyl)-propylamino- acetamidobenzoic acid esters
Ismail, Mohamed Abdel Hamid; Mohamed, Nasser Saad; Dokla, Eman; Khaled A M Abouzid;
Abstract
4-(4-[N-1-carboxy-3-(3,5-dibromo-4-hydroxyphenyl)-3-oxo-propylamino]phenyl) -4-oxo-butyric acid (V), 4-(3- & 4-[N-1-carboxy-3-(3,5-dibromo-4- hydroxyphenyl)-3-oxo-propylaminophenyl]-2-aryl-4-oxo-butyric acids (Xa-e) and 4-(2-alkyl-2-[N-3-(3,5-dibromo-4-hydroxyphenyl)-1-carboxy-3-oxo-propylamino] acetamido) benzoate esters (XVa-e) were designed, synthesized and biologically evaluated as anti-HCV for genotypes 1b and 4a. The design was based on their docking scores with HCV NS3/4A protease-binding site of the genotype 1b (1W3C), which is conserved in the genotype 4a structure. The docking scores predicted that most of these molecules have higher affinity to the HCV NS3/4A enzyme more than Indoline lead. These compounds were synthesized and evaluated for their cytopathic inhibitory activity against RAW HCV cell cultures of genotype 4a and also examined against Huh 5-2 HCV cell culture of genotype 1b, utilizing Luciferase and MTS assays. Compounds Xa and Xb have 95 and 80% of the activity of Ribavirin against genotype 4a and compounds XVa, XVb and XVd exerted high percentage inhibitory activity against genotype 1b equal 87.7, 84.3 and 82.8%, respectively, with low EC50 doses. © 2013 Informa UK, Ltd.
Other data
Title | Ligand design, synthesis and biological anti-HCV evaluations for genotypes 1b and 4a of certain 4-(3- & 4-[3-(3,5-dibromo-4-hydroxyphenyl)-propylamino] phenyl) butyric acids and 3-(3,5-dibromo-4-hydroxyphenyl)-propylamino- acetamidobenzoic acid esters | Authors | Ismail, Mohamed Abdel Hamid; Mohamed, Nasser Saad; Dokla, Eman ; Khaled A M Abouzid | Keywords | Anti-HCV evaluation for genotypes;C-Docker molecular modeling;Conserved binding site's structures of HCV proteases of genotypes 1b and;New anti-HCV prototypes against genotypes;HEPATITIS-C VIRUS;NON-B HEPATITIS;AMINOBENZOIC ACID;NON-A;DERIVATIVES;PROTEIN;DRUG;INHIBITION;POLYMERASE;CHALCONES | Issue Date | 1-Dec-2013 | Publisher | TAYLOR & FRANCIS LTD | Journal | Journal of Enzyme Inhibition and Medicinal Chemistry | Volume | 28 | Issue | 6 | Start page | 1274 | End page | 1290 | ISSN | 1475-6366 | DOI | 10.3109/14756366.2012.733384 | PubMed ID | 23294107 | Scopus ID | 2-s2.0-84887440481 | Web of science ID | WOS:000326745800020 |
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