title: POMA analyses as new efficient bioinformatics' platform to predict and optimise bioactivity of synthesized 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues.
abstract: A series of 43, 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues (D01-D43) were analysed using Petra, Osiris, Molinspiration and ALOGPS (POMA) to identify pharmacophore, toxicity prediction, lipophilicity and bioactivity. All the compounds were evaluated for anti-HIV activity. 3-(4-Chlorophenyl)-N-(4-fluorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D07) was found to be the most active with IC(50)>4.83 μM and CC(50) 4.83 μM. 3-(4-Fluorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carbothioamide (D41) was found to be the most active compound against bacterial strains with MIC of 4 μg/ml, comparable to the standard drug ciprofloxacin while 3-(4-methoxyphenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D38) was found to be the most active compound against fungal strains with MIC 2-4 μg/ml, however less active than standard fluconazole. Toxicities prediction by Osiris were well supported and experimentally verified with exception of some compounds. In anticonvulsant screening, 3-(4-fluorophenyl)-N-(4-chlorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D09) showed maximum activity showing 100% (4/4, 0.25-0.5h) and 75% (3/4, 1.0 h) protection against minimal clonic seizure test without any toxicity.
authors.affiliation: New Drug Discovery Research, Department of Medicinal Chemistry, Alwar Pharmacy College, Alwar, Rajasthan 301 030, India. jawedpharma@gmail.com
authors.forename: Mohamed Jawed
authors.initials: MJ
authors.lastname: Ahsan
authors.forename: Jeyabalan
authors.initials: J
authors.lastname: Govindasamy
authors.forename: Habibullah
authors.initials: H
authors.lastname: Khalilullah
authors.forename: Govind
authors.initials: G
authors.lastname: Mohan
authors.forename: James P
authors.initials: JP
authors.lastname: Stables
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001234:Aspergillus niger / Q000187:drug effects; D001412:Bacillus subtilis / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019295:Computational Biology; D004926:Escherichia coli / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D009043:Motor Activity / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011720:Pyrazoles / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects; D013854:Thioamides / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D000927:Anticonvulsants; D000935:Antifungal Agents; D011720:Pyrazoles; D013854:Thioamides; C031280:pyrazole