Design, Synthesis, and In Vitro Anti‐mycobacterial Activities of Propylene‐Tethered Gatifloxacin‐Isatin Hybrids

• Published in: Journal of heterocyclic chemistry 2018-08, Vol.55 (8), p.1991-1996
• Main Authors: Wang, Hao‐Di, Fan, Yi‐Lei, Zhou, Jing, Xu, Yan, Guan, Jianguo
• Format: Article
• Language: English
• Subjects: Cytotoxicity; Hybrids; Optimization; Propylene; Toxicity; Tuberculosis
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.3227

A series of propylene‐tethered mono‐/bis‐isatin‐gatifloxacin hybrids 3a–f and 4a–f were designed, synthesized, and evaluated for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis (MTB) H37Rv and multidrug‐resistant tuberculosis (MDR‐TB) as well as cytotoxicity against VERO cell line. The results indicated that all hybrids exhibited promising anti‐mycobacterial activities against MTB H37Rv and MDR‐TB with MIC ranging from 0.25 to 16 μg/mL. In particular, the mono‐isatin‐gatifloxacin hybrid 3e (MIC: 0.25 and 0.25 μg/mL) was found to be most active against MTB H37Rv and MDR‐TB strains, which was twofold more active than the parent gatifloxacin (MIC: 0.5 μg/mL) and comparable with rifampicin (RIF) (MIC: 0.25 μg/mL) against MTB H37Rv, and 4‐ > 512 times more potent than the three references gatifloxacin (MIC: 1.0 μg/mL), RIF (MIC: 64 μg/mL), and isoniazid (>128 μg/mL) against MDR‐TB, could act as a starting point for further optimization.