Synthesis and antimycobacterial activities of ring-substituted quinolinecarboxylic acid/ester analogues. Part 1.

Abstract

Structural optimization of recently discovered new chemical entity, 2,8-dicyclopentyl-4-methylquinoline (DCMQ; MIC= 6.25 microg/mL, M. tuberculosis H37Rv) resulted in the synthesis of four new series of ring-substituted quinolinecarboxylic acids/esters constituting 45 analogues. All new derivatives were evaluated for in vitro antimycobacterial activities against M. tuberculosis H37Rv. Certain ring-substituted-2-quinolinecarboxylic acid ester and ring-substituted-2-quinoline acetic acid ester analogues described herein showed moderate to good inhibitory activity. In particular, three analogues methyl 4,5-dicyclopentyl-2-quinolinecarboxylate (3b), methyl 4,8-dicyclopentyl-2-quinolinecarboxylate (3c) and ethyl 2-(2,8-dicyclopentyl-4-quinolyl)acetate (14g) exhibited excellent MIC values of 1.00, 2.00 and 4.00microg/mL, respectively. Results obtained indicate that substitution of the quinoline ring with dicyclopentyl substituent presumably enhances the antimycobacterial activities in the quinoline analogues described herein.

• Authors: Balasubramanian Vaitilingam, Amit Nayyar, Prakash B Palde, Vikramdeep Monga, Rahul Jain, Sukhraj Kaur, Prati Pal Singh
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 12 Issue 15 Pg. 4179-88 (Aug 01 2004) ISSN: 0968-0896 [Print] England
• PMID: 15246094 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Bacterial Agents
• Carboxylic Acids
• Esters
• Quinolines

Topics

• Anti-Bacterial Agents (chemical synthesis, chemistry, pharmacology)
• Carboxylic Acids (chemical synthesis, chemistry, pharmacology)
• Drug Design
• Esters (chemical synthesis, chemistry, pharmacology)
• Microbial Sensitivity Tests
• Molecular Structure
• Mycobacterium tuberculosis (drug effects, genetics)
• Quinolines (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship