School of Chemistry, Monash University, Clayton, Melbourne, Victoria, Australia.
J Inorg Biochem. 2011 Mar;105(3):454-61. doi: 10.1016/j.jinorgbio.2010.08.007. Epub 2010 Aug 19.
Bismuth(III) complexes of NSAIDs (Non-Steroidal Anti Inflammatory Drugs) and substituted benzoic acids (o-methoxybenzoic acid, m-methoxybenzoic acid, o-nitrobenzoic acid, 3,5-diacetamidobenzoic acid, and 5-[(R/S)-2,3-dihydroxypropyl carbamoyl]-2-pyridine carboxylic acid) have been synthesised and fully characterised. Two new bis-carboxylato bismuth complexes have been characterised by single crystal X-ray diffraction, namely [PhBi(o-MeOC(6)H(4)CO(2))(2)(bipy)]·0.5EtOH (bipy=2,2'-bipyridine) and [PhBi(C(9)H(11)N(2)O(3)CO(2))(2)(H(2)O)]·6H(2)O. All compounds were tested against the parasite Leishmania major promastigotes for their anti-Leishmanial activity and were further assessed for their toxicity to mammalian cells. The NSAID free acids and their bismuth derivatives show negligible anti-Leishmanial activity at concentrations 1.95 to 250 μg/mL against the promastigotes of L. major whereas in the case of mammalian cells only bismuth complexes of naproxen and mefenamic acid have significant effect at concentration≥250 μg/mL. The bismuth(III) complexes of substituted benzoic acids show significant anti-Leishmanial activity against the promastigotes of L. major V121 at very low concentrations while their respective free carboxylic acids show no effective activity. However, the bismuth compounds inhibit the growth of the mammalian cells at all concentrations studied (1.95 to 500 μg/mL) following 48 h incubation. The comparatively low toxicity of BiCl(3) and Bi(NO(3))(3), suggests that overall toxicity of bismuth complexes towards the parasite is both ligand and metal dependent.
已合成并充分表征了 NSAIDs（非甾体抗炎药）和取代苯甲酸（邻甲氧基苯甲酸、间甲氧基苯甲酸、邻硝基苯甲酸、3,5-二乙酰氨基苯甲酸和 5-[(R/S)-2,3-二羟基丙基氨甲酰基]-2-吡啶羧酸）的三价铋配合物。通过单晶 X 射线衍射对两种新的双羧基铋配合物进行了表征，即[PhBi(o-MeOC6H4CO2)2(bipy)]·0.5EtOH（bipy=2,2'-联吡啶）和[PhBi(C9H11N2O3CO2)2(H2O)]·6H2O。所有化合物均针对寄生虫利什曼原虫的前鞭毛体进行了抗利什曼原虫活性测试，并进一步评估了它们对哺乳动物细胞的毒性。在浓度为 1.95 至 250μg/mL 时，游离 NSAID 和它们的铋衍生物对利什曼原虫前鞭毛体几乎没有抗利什曼原虫活性，而对于哺乳动物细胞，只有游离萘普生和甲芬那酸的铋复合物在浓度≥250μg/mL 时才有显著作用。取代苯甲酸的铋（III）配合物对利什曼原虫 V121 的前鞭毛体表现出显著的抗利什曼原虫活性，而它们各自的游离羧酸则没有有效活性。然而，在 48 小时孵育后，所有研究浓度（1.95 至 500μg/mL）的铋化合物均抑制了哺乳动物细胞的生长。BiCl3 和 Bi(NO3)3 的相对低毒性表明，铋配合物对寄生虫的总体毒性既依赖于配体又依赖于金属。
