Ring-substituted quinolines as potential anti-tuberculosis agents

• Published in: Bioorganic & medicinal chemistry 2004-05, Vol.12 (10), p.2501-2508
• Main Authors: Vangapandu, Suryanarayana, Jain, Meenakshi, Jain, Rahul, Kaur, Sukhraj, Pal Singh, Prati
• Format: Article
• Language: English
• Subjects: Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antitubercular Agents - chemical synthesis; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacology; Biological and medical sciences; Drug-resistant tuberculosis; Homolytic free radical alkylation; Humans; Medical sciences; Molecular Structure; Mycobacterium tuberculosis - drug effects; Pharmacology. Drug treatments; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - pharmacology; Ring-substituted quinolines; Tuberculosis; Tuberculosis - drug therapy; Tuberculosis, Multidrug-Resistant - drug therapy
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2004.03.045

The anti-tuberculosis activities of ring-substituted quinolines (series 1–4) against drug-sensitive and drug-resistant M. tuberculosis H37Rv strains are described. The most effective analogues have exhibited potent efficacy (MIC= 1.0 μg/mL). We report in vitro antimycobacterial properties of ring-substituted quinolines (series 1–4) constituting 56 analogues against drug-sensitive and drug-resistant M. tuberculosis H37Rv strains. The most effective compounds 2h (R 1=R 2= c-C 6H 11, R 3=NO 2, series 1) and 13g (R 1=OC 7H 15, R 2=NO 2, series 4) have exhibited an MIC value of 1 μg/mL against drug-sensitive M. tuberculosis H37Rv strain that is comparable to first line anti-tuberculosis drug, isoniazid. Selected analogues ( 2d, 2g, 2h, 4e, 6b, 13b, 13g, and 14e, MIC: ⩽6.25 μg/mL) upon further evaluation against single-drug-resistant (SDR) strains of M. tuberculosis H37Rv have produced potent efficacy in the range between 6.25 and 50 μg/mL.