title: Molecular hybridization conceded exceptionally potent quinolinyl-oxadiazole hybrids through phenyl linked thiosemicarbazide antileishmanial scaffolds: In silico validation and SAR studies.
abstract: The high potential of quinoline containing natural products and their derivatives in medicinal chemistry led us to discover a novel series of compounds 6-23 based on the concept of molecular hybridization. Most of the synthesized analogues exhibited potent leishmanicidal potential. The most potent compound (23, IC50=0.10±0.001μM) among the series was found ∼70 times more lethal than the standard drug. The current series 6-23 conceded in the development of fourteen (14) extraordinarily active compounds against leishmaniasis. In silico analysis were also performed to probe the mode of action while all the compounds structure were established by NMR and Mass spectral analysis.
authors.affiliation: Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), PuncakAlam Campus, 42300 Bandar PuncakAlam, 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), PuncakAlam Campus, 42300 Bandar PuncakAlam, Selangor, Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia.
authors.forename: Nor Hadiani
authors.initials: NH
authors.lastname: Ismail
authors.affiliation: Department of Chemistry, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, KPK, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ali
authors.affiliation: Department of Chemistry, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, KPK, Pakistan.
authors.forename: Umer
authors.initials: U
authors.lastname: Rashid
authors.affiliation: Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), PuncakAlam Campus, 42300 Bandar PuncakAlam, Selangor, Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia.
authors.forename: Syahrul
authors.initials: S
authors.lastname: Imran
authors.affiliation: Batterje Medical College for Science & Technology, Jeddah 21442, Saudi Arabia.
authors.forename: Nizam
authors.initials: N
authors.lastname: Uddin
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
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D015195:Drug Design; D006801:Humans; D007891:Leishmania / Q000187:drug effects* / Q000201:enzymology; D007896:Leishmaniasis / Q000188:drug therapy; D062105:Molecular Docking Simulation; D010069:Oxadiazoles / Q000737:chemistry* / Q000494:pharmacology*; D010088:Oxidoreductases / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology; D012663:Semicarbazides / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000981:Antiprotozoal Agents; D010069:Oxadiazoles; D011804:Quinolines; D012663:Semicarbazides; C005151:thiosemicarbazide; C037219:quinoline; D010088:Oxidoreductases; C085592:pteridine reductase
keywords: Antileishmanial; Docking study; Molecular hybridization; Quinolinyl-oxadiazole