基于金(III)的化合物在生理环境中的有限化学稳定性一直是药物发现中的一个挑战。和有机金属化学可能提供解决方案来克服这个问题。在这项工作中,通式结构[(C^N)AuIIIDTC]PF6(C1a-C4a,DTC=二硫代氨基甲酸酯,L1-L4,C^N=2-苯胺并吡啶),并与它们的配位金(III)-二硫代氨基甲酸酯类似物[AuIIIDTCCl2](C1b-C4b)进行比较,作为潜在的抗癌和抗利什曼尼药。大多数复合物有效抑制癌细胞生长,值得注意的是,C3a在纳摩尔范围内对乳腺癌(MCF-7和MDA-MB-231细胞具有中等选择性.对处理的MCF-7细胞的促凋亡研究显示早期凋亡中的大量细胞。C3a对模型硫醇(N-乙酰基-L-半胱氨酸)的反应性研究是指一种可能的作用方式,涉及有机金(III)核心和硫醇盐之间的键合。在被忽视的疾病范围内,金复合物正在成为有希望的治疗利什曼病的替代品。在这方面,所有金(III)-二硫代氨基甲酸盐复合物对至少一种利什曼原虫物种均具有抗利什曼原虫活性。配合物C1a,C4a,C1b,C4b对所有测试的寄生虫都有活性,IC50值在0.12和42μM之间变化。and,总的来说,有机金属化合物呈现更有趣的抑制曲线。对于巴西乳杆菌的C4a选择性超过500倍;甚至高于参考抗利什曼药物两性霉素B。我们的发现表明,相对于配位类似物,有机金(III)部分显着增强了抗癌和抗利什曼原质的作用;因此,显示了有机金属化学在基于金属药物的癌症和利什曼病化疗中的巨大潜力。
The limited chemical stability of gold(III)-based compounds in physiological environment has been a challenge in drug discovery, and organometallic chemistry might provide the solution to overcome this issue. In this work, four novel cationic organogold(III)-dithiocarbamate complexes of general structure [(C^N)AuIIIDTC]PF6 (C1a - C4a, DTC = dithiocarbamate, L1 - L4, C^N = 2-anilinopyridine) are presented, and compared to their coordination gold(III)-dithiocarbamate analogues [AuIIIDTCCl2] (C1b - C4b), as potential anti-cancer and anti-leishmanial drugs. Most of the complexes effectively inhibited cancer cell growth, notably C3a presented anti-proliferative effect in the nanomolar range against breast cancer (MCF-7 and MDA-MB-231 cells with moderate selectivity. Pro-apoptotic studies on treated MCF-7 cells showed a high population of cells in early apoptosis. Reactivity studies of C3a towards model thiols (N-acetyl-L-cysteine) refer to a possible mode of action involving bonding between the organogold(III)-core and the thiolate. In the scope of neglected diseases, gold complexes are emerging as promising therapeutic alternatives against leishmaniasis. In this regard, all gold(III)-dithiocarbamate complexes presented anti-leishmanial activity against at least one Leishmania species. Complexes C1a, C4a, C1b, C4b were active against all tested parasites with IC50 values varying between 0.12 and 42 μM, and, overall, organometallic compounds presented more intriguing inhibition profiles. For C4a selectivity over 500-fold for L. braziliensis; even higher than the reference anti-leishmanial drug amphotericin B. Overall, our findings revealed that the organogold(III) moiety significantly amplified the anti-cancer and anti-leishmanial effects with respect to the coordination analogues; thus, showing the great potential of organometallic chemistry in metallodrug-based chemotherapy for cancer and leishmaniasis.