title: In silico investigation of medicinal spectrum of imidazo-azines from the perspective of multitarget screening against malaria, tuberculosis and Chagas disease.
abstract: A chemical database of 30 representative imidazo-azines was built and screened against important tropical disease targets by computational docking. After three rounds of screening, an interaction profile was generated and analyzed. On the basis of binding energy and ligand efficiency, it was concluded that in general, imidazo-azine scaffold has a potential of being selective and simultaneous inhibitor against the five receptors Pf-dihydrofolate reductase, Pf-enoyl acyl carrier protein reductase, Pf-protein kinase 7, Mt-pantothenate synthetase and Mt-thymidine monophosphate kinase. Interestingly, two compounds 2-(4-chlorophenyl)-N-cyclohexyl-6-methylH-imidazo[1,2-a]pyridine-3-amine (MCL011) and N-cyclohexyl-2-(4-methoxyphenyl)-6-methylH-imidazo[1,2-a]pyridine-3-amine (MCL017) showed highest binding energy against four targets namely Pf-dihydrofolate reductase, Pf-enoyl acyl carrier protein reductase, Pf-protein kinase 7 and Mt-pantothenate synthetase. Eventually, in order to improve the decision making and success rate in actual efficacy evaluations other criteria such as lead-likeness were envisaged.
authors.affiliation: Med. Chem. Lab, Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247 667, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Med. Chem. Lab, Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247 667, India.
authors.forename: Barnita
authors.initials: B
authors.lastname: Makhal
authors.affiliation: Med. Chem. Lab, Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247 667, India.
authors.forename: Vinod Kumar
authors.initials: VK
authors.lastname: Gupta
authors.affiliation: Med. Chem. Lab, Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247 667, India. Electronic address: anujsharma.mcl@gmail.com.
authors.forename: Anuj
authors.initials: A
authors.lastname: Sharma
mesh_terms: D000962:Antimalarials / Q000737:chemistry*; D000995:Antitubercular Agents / Q000737:chemistry*; D014355:Chagas Disease / Q000188:drug therapy*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry; D006801:Humans; D008288:Malaria; D010453:Peptide Synthases / Q000037:antagonists & inhibitors; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D014376:Tuberculosis
chemical_list: D000962:Antimalarials; D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D013762:Tetrahydrofolate Dehydrogenase; D010453:Peptide Synthases; C022318:pantothenate synthetase
keywords: Docking; Imidazo-azines; Lead-likeness; Ligand efficiency; Multitarget screening