Synthesis and biological evaluation of rhodanine derivatives bearing a quinoline moiety as potent antimicrobial agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 23; no. 15; pp. 4358 - 4361
• Main Authors: Guo, Meng, Zheng, Chang-Ji, Song, Ming-Xia, Wu, Yan, Sun, Liang-Peng, Li, Yin-Jing, Liu, Yi, Piao, Hu-Ri
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.08.2013; Elsevier
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - toxicity; Antibacterial activity; antibacterial properties; antibiotics; Cell Survival - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; cytotoxicity; Drug Resistance, Multiple, Bacterial - drug effects; Escherichia coli; Escherichia coli - drug effects; Gram-negative bacteria; Gram-positive bacteria; HeLa Cells; Humans; Life Sciences & Biomedicine; Methicillin-resistant Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus - drug effects; Microbial Sensitivity Tests; minimum inhibitory concentration; multiple drug resistance; Pharmacology & Pharmacy; Physical Sciences; Quinoline; Quinolines - chemistry; Quinolone-resistant Staphylococcus aureus; Rhodanine; Rhodanine - analogs & derivatives; Rhodanine - pharmacology; Rhodanine - toxicity; Science & Technology; Staphylococcus aureus; Structure-Activity Relationship; Rhodanine; Quinoline; Antibacterial activity; Quinolone-resistant Staphylococcus aureus; Methicillin-resistant Staphylococcus aureus; ACID; ANTIBACTERIAL
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2013.05.082

A series of rhodanine derivatives bearing quinoline moiety were designed, synthesized, and evaluated for their anti-bacterial activity. Three series of rhodanine derivatives bearing a quinoline moiety (6a–h, 7a–g, and 8a–e) have been synthesized, characterized, and evaluated as antibacterial agents. The majority of these compounds showed potent antibacterial activities against several different strains of Gram-positive bacteria, including multidrug-resistant clinical isolates. Of the compounds tested, 6g and 8c were identified as the most effective with minimum inhibitory concentration (MIC) values of 1μg/mL against multidrug-resistant Gram-positive organisms, including methicillin-resistant and quinolone-resistant Staphylococcus aureus (MRSA and QRSA, respectively). None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 at 64μg/mL. The cytotoxic activity assay showed that compounds 6g, 7g and 8e exhibited in vitro antibacterial activity at non-cytotoxic concentrations. Thus, these studies suggest that rhodanine derivatives bearing a quinoline moiety are interesting scaffolds for the development of novel Gram-positive antibacterial agents.