title: Synthesis and molecular modelling studies of phenyl linked oxadiazole-phenylhydrazone hybrids as potent antileishmanial agents.
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 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.
authors.affiliation: 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.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Taha
authors.affiliation: 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.
authors.forename: Nor Hadiani
authors.initials: NH
authors.lastname: Ismail
authors.affiliation: 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.
authors.forename: Syahrul
authors.initials: S
authors.lastname: Imran
authors.affiliation: Chemistry Department, College of Sciences and Humanities, Prince Sattam bin Abdulaziz University, Saudi Arabia.
authors.forename: El Hassane
authors.initials: EH
authors.lastname: Anouar
authors.affiliation: 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.
authors.forename: Manikandan
authors.initials: M
authors.lastname: Selvaraj
authors.affiliation: Institute of Advance Research Studies in Chemical Sciences, University of Sindh Jamshoro, 76080 Hyderabad, Pakistan.
authors.forename: Waqas
authors.initials: W
authors.lastname: Jamil
authors.affiliation: Department of Chemistry, COMSATS Institute of Information Technology, University Road, Abbottbad 22060, KPK, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ali
authors.affiliation: Institute of Advance Research Studies in Chemical Sciences, University of Sindh Jamshoro, 76080 Hyderabad, Pakistan.
authors.forename: Syed Muhammad
authors.initials: SM
authors.lastname: Kashif
authors.affiliation: Depatment of Chemistry, Hazara University, Mansehra, Pakistan.
authors.forename: Fazal
authors.initials: F
authors.lastname: Rahim
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Khalid Mohammed
authors.initials: KM
authors.lastname: Khan
authors.affiliation: 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.
authors.forename: Mohd Ilham
authors.initials: MI
authors.lastname: Adenan
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007891:Leishmania / Q000187:drug effects* / Q000201:enzymology; D062105:Molecular Docking Simulation; D010069:Oxadiazoles / Q000737:chemistry*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D006835:Hydrazones; D010069:Oxadiazoles; C012483:phenylhydrazone; D010088:Oxidoreductases; C085592:pteridine reductase
keywords: DFT; Leishmaniasis; Molecular docking studies; Oxadiazole-benzohydrazone hybrids; SAR study; Selectivity index