Design, Synthesis and In VitroIn Vitro Anti‐mycobacterial Activities of 8‐ OMeOMe Ciprofloxacin‐1 H HH ‐1,2,3‐triazole‐isatin‐(thio) Semicarbazide/Oxime Hybrids

摘要

> A series of novel 8‐OMe ciprofloxacin (8‐OMe CPFX)‐1 H ‐1,2,3‐triazole‐isatin‐(thio) semicarbazide/oxime hybrids 6a – l with the capacity to form hydrogen bond were designed, synthesized, and evaluated for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis (MTB) H ₃₇ Rv and MDR‐TB as well as cytotoxicity. All the synthesized hybrids (MIC: 0.39–16?μg/mL) exhibited excellent activities against MTB H ₃₇ Rv and MDR‐TB, and the majority of them were more potent than the parent 8‐OMe CPFX (MIC: 1.56 and 2.0?μg/mL, respectively). In particular, the most active conjugate 6h (MIC: 0.39 and 1.0?μg/mL, respectively) was two to eight times more potent in vitro than the references CPFX (MIC: 3.12 and 4.0?μg/mL, respectively) and 8‐OMe CPFX against the tested strains and was comparable with or 64‐folds more potent than RIF (MIC: 0.39 and 64?μg/mL, respectively) against MTB H ₃₇ Rv and MDR‐TB, respectively. In addition, all conjugates (CC ₅₀ : 16–64?μg/mL) showed acceptable cytotoxicity, although most of them were more toxic than the parent (CC ₅₀ : 64?μg/mL) in VERO cell line.