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: Mohamed Jawed Ahsan, Jeyabalan Govindasamy, Habibullah Khalilullah, Govind Mohan, James P Stables
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 22 Issue 23 Pg. 7029-35 (Dec 01 2012) ISSN: 1464-3405 [Electronic] England
• PMID: 23099090 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Amides
• Anti-Bacterial Agents
• Anti-HIV Agents
• Anticonvulsants
• Antifungal Agents
• Pyrazoles
• Thioamides
• pyrazole

Topics

• Amides (chemical synthesis, chemistry)
• Animals
• Anti-Bacterial Agents (chemical synthesis, chemistry, pharmacology)
• Anti-HIV Agents (chemistry, pharmacology, toxicity)
• Anticonvulsants (chemical synthesis, chemistry, pharmacology)
• Antifungal Agents (chemical synthesis, chemistry, pharmacology)
• Aspergillus niger (drug effects)
• Bacillus subtilis (drug effects)
• Candida albicans (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Computational Biology
• Escherichia coli (drug effects)
• HIV-1 (drug effects)
• HIV-2 (drug effects)
• Humans
• Mice
• Microbial Sensitivity Tests
• Motor Activity (drug effects)
• Pseudomonas aeruginosa (drug effects)
• Pyrazoles (chemistry)
• Staphylococcus aureus (drug effects)
• Thioamides (chemical synthesis, chemistry)