Molecular design and synthesis of HCV inhibitors based on thiazolone scaffold.
A series of thiazolone derivatives was designed and synthesized as potential HCV NS5B allosteric polymerase inhibitors at the allosteric site thumb II. Their antiviral activity was evaluated and molecular modeling was utilized to give further envision on their probable binding modes in the allosteric binding site. Among the tested molecules, compound 9b displayed sub-micromolar inhibitory activity with an EC50 of 0.79 μM indicating excellent potency profile. It also showed good safety profile (CC50≥75 μM and SI≥94.3).
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
Ghada H
GH
Al-Ansary
Mohamed A H
MA
Ismail
Dalal A
DA
Abou El Ella
Sameh
S
Eid
Khaled A M
KA
Abouzid
D000495:Allosteric Site; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D015195:Drug Design; D016174:Hepacivirus / Q000187:drug effects*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D013844:Thiazoles; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
Glide docking; HCV; HCV NS5B inhibitor; Sulfonamide derivatives; Thiazole