Synthesis and molecular modelling studies of phenyl linked oxadiazole-phenylhydrazone hybrids as potent antileishmanial agents
作者:Muhammad Taha、Nor Hadiani Ismail、Syahrul Imran、El Hassane Anouar、Manikandan Selvaraj、Waqas Jamil、Muhammad Ali、Syed Muhammad Kashif、Fazal Rahim、Khalid Mohammed Khan、Mohd Ilham Adenan
DOI:10.1016/j.ejmech.2016.12.019
日期:2017.1
Molecular hybridization yielded phenyl linked oxadiazole-benzohydrazones hybrids 6-35 and were evaluated for their antileishmanial potentials. Compound 10, a 3,4-dihydroxy analog with IC50 value of 0.95 +/- 0.01 mu M, was found to be the most potent antileishmanial agent (7 times more active) than the standard drug pentamidine (IC50 = 7.02 +/- 0.09 mu M). The current series 6-35 conceded in the identification of thirteen (13) potent antileishmanial compounds with the IC50 values ranging between 0.95 +/- 0.01-78.6 +/- 1.78 mu M. Molecular docking analysis against pteridine reductase (PTR1) were also performed to probe the mode of action. Selectivity index showed that compounds with higher number of hydroxyl groups have low selectivity index. Theoretical stereochemical assignment was also done for certain derivatives by using density functional calculations. (C) 2016 Elsevier Masson SAS. All rights reserved.