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A series of novel propylene‐1H‐1,2,3‐triazole‐4‐methylene‐tethered isatin‐coumarin hybrids 7a–l that were composed of three anti‐tubercular bioactive substances/pharmacophore coumarin, isatin, and I‐A09 were designed, synthesized, and assessed for their in vitro anti‐tubercular activity against Mycobacterium tuberculosis (MTB) H37Rv. In spite of the hybrids were inactive against the tested MTB H37Rv, the structure–activity relationship was enriched, and these hybrids may act as an ideal starting point for developing new isatin‐coumarin anti‐TB candidates with various linkers. [ABSTRACT FROM AUTHOR]

A set of propylene‐tethered isatin dimmers 2a–i was synthesized via click chemistry and screened for their in vitro antimycobacterial activities against Mycobacterium tuberculosis (MTB) H37Rv and multidrug‐resistant TB. In spite of all dimmers (minimum inhibitory concentration: 25– > 128 μg/mL) only exhibited weak to moderate activities against the tested MTB H37Rv and multidrug‐resistant TB, the structure–activity relationship was enriched and the results warrant further development of the anti‐TB properties of this kind of dimmers. [ABSTRACT FROM AUTHOR]

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 H37Rv and multidrug‐resistant tuberculosis. The results showed that all the synthesized hybrids [minimum inhibitory concentration (MIC): 0.25–4.0 μg/mL] displayed considerable activities against the tested two strains, but all less active than the parent moxifloxacin (MIC: 0.10 and 0.12 μg/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 5 g was found most active against Mycobacterium tuberculosis H37Rv with MIC of 0.39 μg/mL, which was comparable with rifampicin (MIC: 0.39 μg/mL), while conjugate 5a (MIC: 0.25 μg/mL) was 128– > 512 times more active than rifampicin (MIC: 32 μg/mL) and isoniazid (MIC: >128 μg/mL) against multidrug‐resistant tuberculosis. [ABSTRACT FROM AUTHOR]

A new class of isatin‐1,2,3‐triazole‐moxifloxacin (MXFX) hybrids 5a–j was designed, synthesized, and screened for their in vitro antimycobacterial activities against Mycobacterium tuberculosis H37Rv and MDR‐TB. All the synthesized hybrids (MIC: 0.10–0.78 μg/mL) exhibited excellent activities against MTB H37Rv and MDR‐TB, in spite of none of them were more potent than the parent MXFX (MIC: 0.10 and 0.12 μg/mL). Against MTB H37Rv, the most active 5f (MIC: 0.10 μg/mL) was comparable with MXFX and 4 times more potent than RIF (MIC: 0.39 μg/mL). Against MDR‐TB, all hybrids were more active than RIF (MIC: 32 μg/mL) and INH (MIC: >128 μg/mL). In particular, hybrid 5e (MIC: 0.10 μg/mL) was comparable with MXFX and 256 and >1,024 times more potent than RIF and INH. Both conjugates 5e and 5f warrant further investigations. [ABSTRACT FROM AUTHOR]

Eight novel 1 H-1,2,3-triazole-tethered ciprofloxacin (CPFX) isatin conjugates 5a- h with greater lipophilicity compared with CPFX were designed, synthesized, and evaluated for their in vitro anti-mycobacterial activity against Mycobacterium smegmatis and Mycobacterium tuberculosis (MTB) H37Rv. The preliminary results showed that all hybrids (MIC: 12.5-100 μg/mL) exhibited considerable activity against M. smegmatis, but less active than the parent CPFX (MIC: 6.25 μg/mL) and the reference INH (MIC: 0.78 μg/mL). Against MTB H37Rv, all hybrids displayed excellent inhibitory activity with MICs ranging from 1.56 to 25 μg/mL, particularly, 5h (MIC: 1.56 μg/mL) was twofold more active CPFX (MIC: 3.12 μg/mL), warrant further investigations. [ABSTRACT FROM AUTHOR]