Title of article :
Design, Synthesis, Molecular Modeling Studies and Biological Evaluation of N′-Arylidene-6-(benzyloxy)-4-oxo-1,4-dihydroquinoline-3- carbohydrazide Derivatives as Novel Anti-HCV Agents
Author/Authors :
Mahboobi rabbani, Mohammad Ismaeil Department of Pharmaceutical Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences, Tehran, Iran , Vahabpour Rodsari, Roholah Department of Medical Lab Technology - School of Allied Medical Sciences - Shahid Beheshti University of Medical Sciences, Tehran, Iran , Hajimahdi, Zahra Department of Pharmaceutical Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences, Tehran, Iran , Zarghi, Afshin Department of Pharmaceutical Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract :
HCV-induced hepatitis is one of the most debilitating diseases. The limited number of anti-
HCV drugs and drug-resistance necessitate developing of new scaffolds with different mode
of actions. HCV non-structural protein 5B (NS5B) is an attractive target for development of
novel inhibitors of HCV replication. In this paper, new N′-arylidene-6-(benzyloxy)-4-oxo-1,4-
dihydroquinoline-3-carbohydrazide derivatives were designed based on the pharmacophores
of HCV NS5B active site binding inhibitors. Designed compounds were synthesized and
evaluated for their inhibitory activities in a cell-based HCV replicon system assay. Among
tested compounds, compounds 18 and 20 were found to be the most active (EC50 = 35
and 70 μM, respectively) with good selectivity index (SI > 2) in the corresponding series.
Molecular modeling studies showed that the designed compounds are capable of forming key
coordination with the two magnesium ions as well as interactions with other key residues at
the active site of HCV NS5B.
Keywords :
Molecular modeling studies , NS5B polymerase , HCV , 4-dihydroquinoline-3-carbohydrazide , Design, 4-Oxo-1 , Synthesis
Journal title :
Astroparticle Physics
