Agents that selectively target the mycobacterial membrane could potentially shorten treatment time for tuberculosis, reduce relapse, and curtail emergence of resistant strains. The lipophilicity and extensive charge-delocalized state of the triphenylphosphonium cation strongly favor accumulation within bacterial membranes. Here, we explored the antimycobacterial activities and membrane-targeting properties of indolylalkyltriphenylphosphonium analogues. The most active analogues preferentially inhibited growth of Mycobacterium tuberculosis H37Rv (MIC₅₀ 2–4 μM) and were bactericidal against Mycobacterium bovis BCG (MBC₉₉ 3 μM). In spite of their propensity to accumulate within membranes, we found no evidence that these compounds permeabilized mycobacterial membranes or induced cell-envelope stress. Our investigations indicated that their bacterical effects stem from sustained depolarization of mycobacterial membranes and ensuing disruptive effects on electron transfer and cell division.

中文翻译：

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吲哚基烷基三苯基phosph类似物是膜去极化的分枝杀菌剂。

选择性靶向分枝杆菌膜的药物可能会缩短结核病的治疗时间，减少复发并减少耐药菌株的出现。三苯基phosph阳离子的亲脂性和广泛的电荷离域状态强烈促进细菌膜内的积累。在这里，我们探讨了吲哚基烷基三苯基phosph类似物的抗分枝杆菌活性和膜靶向性能。最活跃的类似物优先抑制结核分枝杆菌H37Rv（MIC ₅₀ 2–4μM）的生长，并且对牛分枝杆菌BCG（MBC ₉₉）具有杀菌作用3μM）。尽管它们倾向于在膜内积累，但我们没有发现这些化合物能渗透分枝杆菌膜或引起细胞包膜应力的证据。我们的研究表明，它们的细菌作用源于分枝杆菌膜的持续去极化以及随之而来的对电子转移和细胞分裂的破坏作用。