A One Pot Synthesis of Novel Bioactive Tri-Substitute-Condensed-Imidazopyridines that Targets Snake Venom Phospholipase A2

• Published in: PloS one Vol. 10; no. 7; p. e0131896
• Main Authors: Anilkumar, Nirvanappa C, Sundaram, Mahalingam S, Mohan, Chakrabhavi Dhananjaya, Rangappa, Shobith, Bulusu, Krishna C, Fuchs, Julian E, Girish, Kesturu S, Bender, Andreas, Basappa, Rangappa, Kanchugarakoppal S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.07.2015; Public Library of Science (PLoS)
• Subjects: Acids; Affinity; Animals; Aromatic compounds; Bioavailability; Biochemistry; Biological activity; Biology; Chemistry; College campuses; Daboia; Drugs; Group II Phospholipases A2 - antagonists & inhibitors; Group II Phospholipases A2 - chemistry; Informatics; Laboratories; Liver cancer; Molecular docking; Molecular Docking Simulation; Nimesulide; Pharmaceutical sciences; Phospholipase; Phospholipase A2; Phospholipase A2 Inhibitors - chemical synthesis; Phospholipase A2 Inhibitors - chemistry; Proteins; Pyridines; Pyridines - chemical synthesis; Pyridines - chemistry; Scaffolds; Studies; Synthesis; Venom; Viper Venoms; Zolpidem
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0131896

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.