School of Chemistry, Monash University, P.O. Box 23, Melbourne, Victoria 3800, Australia.
Dalton Trans. 2014 Jan 21;43(3):1279-91. doi: 10.1039/c3dt52544a. Epub 2013 Nov 5.
Nine different β-thioxoketones of general formula R(1)C(=O)CH2C(=S)R(2) (R(1) = C6H5, R(2) = C6H5L1; R(1) = C6H5, R(2) = p-CF3C6H4L2; R(1) = p-MeOC6H4, R(2) = C6H5L3; R(1) = p-MeOC6H4, R(2) = p-CF3C6H4L4; R(1) = C5H4N, R(2) = C6H5L5; R(1) = p-IC6H4, R(2) = C6H5L6; R(1) = C6H5, R(2) = p-IC6H4L7; R(1) = C6H5, R(2) = C10H7L8 and R(1) = CH3, R(2) = C6H5L9) and their tris-substituted bismuth(III) complexes having the general formula [Bi{R(1)C(=O)CHC(=S)R(2)}3] were synthesised and fully characterised. The solid state structure of [Bi{C5H4NC(=O)CHC(=S)C6H5}3] B5 was determined by crystallography and revealed that the three β-thioxoketonato ligands are bound to bismuth(III) centre in a bidentate fashion through O and S atoms. The bismuth(III) complexes and the corresponding thioxoketones were assessed for their activity against H. pylori. All of the bismuth(III) complexes were highly active against H. pylori having a MIC of greater than or equal to 3.125 μg mL(-1), while the free acids were essentially not toxic to the bacteria. The anti-leishmanial activity of all the bismuth(III) β-thioxoketonates and the corresponding free acids were assessed against L. major promastigotes. The toxicity towards human fibroblast cells was also assessed. All of the free β-thioxoketones were selectively toxic to the L. major promastigotes displaying some potential as anti-leishmanial agents. Among these [C6H5C(=O)CH2C(=S)C6H5] L1 and [C5H4NC(=O)CH2C(=S)C6H5] L5 showed comparable activity to that of Amphotericin B, killing about 80% of the L. major promastigotes at a concentration of 25 μM (6.0 μg mL(-1)). The bismuth(III) β-thioxoketonate complexes were toxic to both the L. major promastigotes and fibroblast cells at high concentrations, but gave no improvement in anti-leishmanial activity over the free β-thioxoketones.
九种不同的β-硫代酮，通式为 R(1)C(=O)CH2C(=S)R(2)（R(1) = C6H5，R(2) = C6H5L1；R(1) = C6H5，R(2) = p-CF3C6H4L2；R(1) = p-MeOC6H4，R(2) = C6H5L3；R(1) = p-MeOC6H4，R(2) = p-CF3C6H4L4；R(1) = C5H4N，R(2) = C6H5L5；R(1) = p-IC6H4，R(2) = C6H5L6；R(1) = C6H5，R(2) = p-IC6H4L7；R(1) = C6H5，R(2) = C10H7L8 和 R(1) = CH3，R(2) = C6H5L9）及其三取代的三价铋（III）配合物，通式为[Bi{R(1)C(=O)CHC(=S)R(2)}3]，被合成并进行了全面表征。[Bi{C5H4NC(=O)CHC(=S)C6H5}3]B5 的固体结构通过晶体学确定，结果表明三个β-硫代酮配体通过 O 和 S 原子以双齿配位方式与铋（III）中心结合。三价铋（III）配合物和相应的硫代酮被评估了对 H. pylori 的活性。所有的三价铋（III）配合物对 H. pylori 均具有高度活性，MIC 大于或等于 3.125 μg mL(-1)，而游离酸对细菌基本没有毒性。所有三价铋（III）β-硫代酮和相应的游离酸的抗利什曼原虫活性都进行了评估。还评估了它们对人成纤维细胞的毒性。所有游离的β-硫代酮对 L. major 前鞭毛体具有选择性毒性，显示出一定的作为抗利什曼原虫药物的潜力。其中，[C6H5C(=O)CH2C(=S)C6H5]L1 和 [C5H4NC(=O)CH2C(=S)C6H5]L5 与两性霉素 B 的活性相当，在 25 μM（6.0 μg mL(-1)）的浓度下杀死了大约 80%的 L. major 前鞭毛体。三价铋（III）β-硫代酮配合物在高浓度时对 L. major 前鞭毛体和成纤维细胞均有毒性，但在抗利什曼原虫活性方面并没有优于游离的β-硫代酮。
