Tetraethylene Glycol Tethered Heteronuclear Bis-isatin Derivatives: Design, Synthesis, and In Vitro Anti-mycobacterial Activities

A series of novel tetraethylene glycol tethered heteronuclear bis-isatin derivatives 7a-l were designed, synthesized, and evaluated for their in vitro anti-mycobacterial activities against Mycobacterium tuberculosis (MTB) H37Rv and multidrug-resistant TB (MDR-TB) as well as cytotoxicity in VERO cell line. All hybrids exhibited potential anti-mycobacterial activities against MTB H37Rv and MDR-TB, and acceptable cytotoxicity. Among them, the heteronuclear bis-isatin 7l [minimum inhibitory concentration (MIC): 16 and 16g/mL] was found to be most active against MTB H37Rv and MDR-TB strains, which was 2-fold and >8-fold, respectively, more potent than were the first-line anti-tubercular agents rifampicin (MIC: 32g/mL) and isoniazid (MIC: >128g/mL) against MDR-TB, also demonstrated acceptable cytotoxicity profile (CC50: 62.5g/mL), could act as a starting point for further optimization.