title: A One Pot Synthesis of Novel Bioactive Tri-Substitute-Condensed-Imidazopyridines that Targets Snake Venom Phospholipase A2.
abstract: Drugs such as necopidem, saripidem, alpidem, zolpidem, and olprinone contain nitrogen-containing bicyclic, condensed-imidazo[1,2-α]pyridines as bioactive scaffolds. In this work, we report a high-yield one pot synthesis of 1-(2-methyl-8-aryl-substitued-imidazo[1,2-α]pyridin-3-yl)ethan-1-onefor the first-time. Subsequently, we performed in silico mode-of-action analysis and predicted that the synthesized imidazopyridines targets Phospholipase A2 (PLA2). In vitro analysis confirmed the predicted target PLA2 for the novel imidazopyridine derivative1-(2-Methyl-8-naphthalen-1-yl-imidazo [1,2-α]pyridine-3-yl)-ethanone (compound 3f) showing significant inhibitory activity towards snake venom PLA2 with an IC50 value of 14.3 μM. Evidently, the molecular docking analysis suggested that imidazopyridine compound was able to bind to the active site of the PLA2 with strong affinity, whose affinity values are comparable to nimesulide. Furthermore, we estimated the potential for oral bioavailability by Lipinski's Rule of Five. Hence, it is concluded that the compound 3f could be a lead molecule against snake venom PLA2.
authors.affiliation: Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Central College campus, Palace Road, Bangalore-560 001, Karnataka, India.
authors.forename: Nirvanappa C
authors.initials: NC
authors.lastname: Anilkumar
authors.affiliation: Department of Studies in Biochemistry, University of Mysore, Mysore-570 006, Karnataka, India.
authors.forename: Mahalingam S
authors.initials: MS
authors.lastname: Sundaram
authors.affiliation: Department of Studies in Chemistry, University of Mysore, Mysore-570 006, Karnataka, India.
authors.forename: Chakrabhavi Dhananjaya
authors.initials: CD
authors.lastname: Mohan
authors.affiliation: Frontier Research Center for Post-genome Science and Technology Hokkaido University, Sapporo, 060-0808, Japan.
authors.forename: Shobith
authors.initials: S
authors.lastname: Rangappa
authors.affiliation: Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, United Kingdom.
authors.forename: Krishna C
authors.initials: KC
authors.lastname: Bulusu
authors.affiliation: Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, United Kingdom.
authors.forename: Julian E
authors.initials: JE
authors.lastname: Fuchs
authors.affiliation: Department of Studies in Biochemistry, University of Mysore, Mysore-570 006, Karnataka, India; Department of Studies and Research in Biochemistry, Tumkur University, Tumkur-572 103, Karnataka, India.
authors.forename: Kesturu S
authors.initials: KS
authors.lastname: Girish
authors.affiliation: Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, United Kingdom.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bender
authors.affiliation: Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Central College campus, Palace Road, Bangalore-560 001, Karnataka, India.
authors.lastname: Basappa
authors.affiliation: Department of Studies in Chemistry, University of Mysore, Mysore-570 006, Karnataka, India.
authors.forename: Kanchugarakoppal S
authors.initials: KS
authors.lastname: Rangappa
mesh_terms: D000818:Animals; D054501:Group II Phospholipases A2 / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D062105:Molecular Docking Simulation; D064801:Phospholipase A2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry; D017840:Daboia; D014757:Viper Venoms
chemical_list: D064801:Phospholipase A2 Inhibitors; D011725:Pyridines; D014757:Viper Venoms; D054501:Group II Phospholipases A2; C408444:VRV-PL-VIIIa phospholipase A2, Vipera russelli