Design, Synthesis and In Vitro Anti-mycobacterial Activity of Propylene-1H-1,2,3-triazole-4-methylene-tethered Isatin-moxifloxacin Hybrids

Ten propylene-1H-1,2,3-triazole-4-methylene-tethered isatin-moxifloxacin hybrids 5a-j were synthesized via Cu-promoted azide-alkyne cycloaddition reaction, and screened for their in vitro anti-mycobacterial activities against Mycobacterium tuberculosis H(37)Rv and multidrug-resistant tuberculosis. The results showed that all the synthesized hybrids [minimum inhibitory concentration (MIC): 0.25-4.0g/mL] displayed considerable activities against the tested two strains, but all less active than the parent moxifloxacin (MIC: 0.10 and 0.12g/mL). The resistance index of the most targets was around 1, suggesting this kind of hybrids could reduce the cross-resistance to some extent. Among them, hybrid 5g was found most active against Mycobacterium tuberculosis H(37)Rv with MIC of 0.39g/mL, which was comparable with rifampicin (MIC: 0.39g/mL), while conjugate 5a (MIC: 0.25g/mL) was 128->512 times more active than rifampicin (MIC: 32g/mL) and isoniazid (MIC: >128g/mL) against multidrug-resistant tuberculosis.