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

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 16g/mL. In particular, the mono-isatin-gatifloxacin hybrid 3e (MIC: 0.25 and 0.25g/mL) was found to be most active against MTB H(37)Rv and MDR-TB strains, which was twofold more active than the parent gatifloxacin (MIC: 0.5g/mL) and comparable with rifampicin (RIF) (MIC: 0.25g/mL) against MTB H(37)Rv, and 4- > 512 times more potent than the three references gatifloxacin (MIC: 1.0g/mL), RIF (MIC: 64g/mL), and isoniazid (>128g/mL) against MDR-TB, could act as a starting point for further optimization.