Tuberculosis has remained one of the world's deadliest infectious diseases. The complexity and numerous adverse effects of current treatment options as well as the emergence of multi-drug resistant M. tuberculosis (Mtb) demand research and innovation efforts to yield new anti-mycobacterial agents. In this study, we synthesized a series of imidazo[1,5-a]quinolines, including 4 new analogs, and evaluated their activity against Mtb. Inspired by previous studies, we also designed 8 compounds featuring a coordinated metal ion, determined their absolute configuration by single-crystal X-ray diffraction and included them in the bioactivity study. Remarkably, the metal complexation of 5c with either Zn²⁺ or Fe²⁺ increased the Mtb inhibitory activity of the compound 12.5-fold and reduced its cytotoxicity. Ultimately, out of the 21 analyzed imidazo[1,5-a]quinoline analogs, two zinc complexes (C1 and C7) showed the strongest, specific activity against Mtb H37Rv in vitro (IC₉₀ = 7.7 and 17.7 μM).

中文翻译：

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咪唑并[1,5-a]喹啉及其锌配合物的设计、合成及其抗分枝杆菌活性

结核病仍然是世界上最致命的传染病之一。当前治疗方案的复杂性和众多副作用以及多重耐药结核分枝杆菌(Mtb) 的出现，需要研究和创新努力来产生新的抗分枝杆菌药物。在这项研究中，我们合成了一系列咪唑并[1,5- a ]喹啉，包括4种新的类似物，并评估了它们对结核分枝杆菌的活性。受前期研究的启发，我们还设计了8种具有配位金属离子的化合物，通过单晶X射线衍射确定了它们的绝对构型，并将其纳入生物活性研究。值得注意的是， 5c与 Zn ²⁺或 Fe ²⁺的金属络合使该化合物的 Mtb 抑制活性提高了 12.5 倍，并降低了其细胞毒性。最终，在分析的 21 种咪唑并[1,5- a ]喹啉类似物中，两种锌复合物（C1和C7 ）在体外表现出最强的针对 Mtb H37Rv 的特异性活性（IC ₉₀ = 7.7 和 17.7 μM）。