Synthesis and molecular modelling studies of phenyl linked oxadiazole-phenylhydrazone hybrids as potent antileishmanial agents

• Published in: European Journal of Medicinal Chemistry
• Main Author: Taha M.; Ismail N.H.; Imran S.; Anouar E.H.; Selvaraj M.; Jamil W.; Ali M.; Kashif S.M.; Rahim F.; Khan K.M.; Adenan M.I.
• Format: Article
• Language: English
• Published: Elsevier Masson SAS 2017
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85006802382&doi=10.1016%2fj.ejmech.2016.12.019&partnerID=40&md5=715f0059120195ba1e75dba8e4ebe2d3

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 IC50value of 0.95 ± 0.01 μM, was found to be the most potent antileishmanial agent (7 times more active) than the standard drug pentamidine (IC50= 7.02 ± 0.09 μM). The current series 6–35 conceded in the identification of thirteen (13) potent antileishmanial compounds with the IC50values ranging between 0.95 ± 0.01–78.6 ± 1.78 μM. 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. © 2016 Elsevier Masson SAS