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

Taha M 1 , Ismail NH 2 , Imran S 2 , Anouar EH 3 , Selvaraj M 4 , Jamil W 5 Show all authors , Ali M 6 , Kashif SM 5 , Rahim F 7 , Khan KM 8 , Adenan MI 2

Affiliations 

  • 1 Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia. Electronic address: taha_hej@yahoo.com
  • 2 Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia
  • 3 Chemistry Department, College of Sciences and Humanities, Prince Sattam bin Abdulaziz University, Saudi Arabia
  • 4 Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia; Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia
  • 5 Institute of Advance Research Studies in Chemical Sciences, University of Sindh Jamshoro, 76080 Hyderabad, Pakistan
  • 6 Department of Chemistry, COMSATS Institute of Information Technology, University Road, Abbottbad 22060, KPK, Pakistan
  • 7 Depatment of Chemistry, Hazara University, Mansehra, Pakistan
  • 8 H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Eur J Med Chem, 2017 Jan 27;126:1021-1033.
PMID: 28012342 DOI: 10.1016/j.ejmech.2016.12.019

Abstract

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 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 IC50 values 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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