Loh Allan, Ong Yih Ching, Blair Victoria L, Kedzierski Lukasz, Andrews Philip C
School of Chemistry, Monash University, Clayton, Melbourne, VIC, 3800, Australia.
Walter and Eliza Institute of Medical Research, Parkville, Melbourne, VIC, 3052, Australia.
J Biol Inorg Chem. 2015 Oct;20(7):1193-203. doi: 10.1007/s00775-015-1299-6. Epub 2015 Sep 28.
Eight bismuth(III) complexes derived from the simple α-hydroxycarboxylic acids; gluconic (H₆-glu), tartaric (H₄-tar), mandelic (H₂-man), malic (H₃-mal) and glycolic (H₂-gly) have been synthesised and characterised. The complexes are formed through direct treatment of the organic acids with Bi(NO₃)3·5H₂O ([Bi(H₂-tar)(H₃- tar)] 2, [Bi(mal)(NO₃)(H₂O)₂] 6, [Bi(gly)(NO₃)(H₂O)] 8) or Bi(OtBu)₃ ([Bi(H-tar)(H₂O)₂] 1, [Bi(man)(H-man) (H₂O)] 4, [Bi2(H-mal)₃] 5, [Bi(gly)(H-gly)] 7), or through metathesis of the sodium salts with Bi(NO₃)3·5H₂O ([Bi(H3-glu)]₃). Reactions with both glucuronic and mucic acid proved to be unsuccessful. Small crystals of [Bi(gly)4(NO₃)4(H₂O)₄]·5H₂O 8 were obtained from aqueous solution and analysed by synchrotron X-ray diffraction. The data were relatively poor but composition and connectivity were established, confirming and supporting other analyses. Those complexes which displayed sufficient solubility; 2, 4, 7 and 8, were tested for their anti-Leishmanial activity against parasite promastigotes and amastigotes, and for toxicity against human fibroblast cells. All four complexes and their parent acids showed no toxicity towards either the promastigotes or fibroblast cells. However, the two glycolate complexes showed selective toxicity towards amastigotes with complex 8 providing for a low % viability of 1.8 ± 0.9 at 50.0 μM. Graphical Abstract Novel bismuth(III) complexes derived from α-hydroxycarboxylic acids have been synthesised, characterised and assessed for their anti-leishmanial activity. The glycolate complexes are selectively toxic against parasite amastigotes, with all complexes being nontoxic towards promastigotes and human fibroblast cells.
已合成并表征了八种由简单α-羟基羧酸衍生而来的铋（III）配合物；葡萄糖酸（H₆-葡糖酸）、酒石酸（H₄-酒石酸）、扁桃酸（H₂-扁桃酸）、苹果酸（H₃-苹果酸）和乙醇酸（H₂-乙醇酸）。这些配合物是通过用Bi(NO₃)₃·5H₂O（[Bi(H₂-酒石酸)(H₃-酒石酸)] 2、[Bi(苹果酸)(NO₃)(H₂O)₂] 6、[Bi(乙醇酸)(NO₃)(H₂O)] 8）或Bi(OtBu)₃（[Bi(H-酒石酸)(H₂O)₂] 1、[Bi(扁桃酸)(H-扁桃酸)(H₂O)] 4、[Bi₂(H-苹果酸)₃] 5、[Bi(乙醇酸)(H-乙醇酸)] 7）直接处理有机酸形成的，或者通过钠盐与Bi(NO₃)₃·5H₂O（[Bi(H₃-葡萄糖酸)]₃）的复分解反应形成。事实证明，与葡糖醛酸和粘酸的反应均未成功。从水溶液中获得了[Bi(乙醇酸)₄(NO₃)₄(H₂O)₄]·5H₂O 8的小晶体，并通过同步加速器X射线衍射进行了分析。数据相对较差，但确定了组成和连接性，证实并支持了其他分析。对那些具有足够溶解度的配合物；2、4、7和8，测试了它们对寄生虫前鞭毛体和无鞭毛体的抗利什曼原虫活性以及对人成纤维细胞的毒性。所有四种配合物及其母体酸对前鞭毛体或成纤维细胞均无毒性。然而，两种乙醇酸配合物对无鞭毛体表现出选择性毒性，配合物8在50.0 μM时的活力低至1.8±0.9%。图形摘要已合成、表征并评估了由α-羟基羧酸衍生而来的新型铋（III）配合物的抗利什曼原虫活性。乙醇酸配合物对寄生虫无鞭毛体具有选择性毒性，所有配合物对前鞭毛体和人成纤维细胞均无毒。
