Laboratory of Inorganic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Laboratory of Pharmacology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece.
Molecules. 2023 Jan 1;28(1):336. doi: 10.3390/molecules28010336.
Ag(I) coordination compounds have recently attracted much attention as antiproliferative and antibacterial agents against a wide range of cancer cell lines and pathogens. The bioactivity potential of these complexes depends on their structural characteristics and the nature of their ligands. Herein, we present a series of four Ag(I) coordination compounds bearing as ligands the CH-substituted thiadiazole-based thioamide 5-methyl-1,3,4-thiadiazole-2-thiol (mtdztH) and phosphines, i.e., [AgCl(mtdztH)(PPh)] (), [Ag(mtdzt)(PPh)] (), [AgCl(mtdztH)(xantphos)] (), and [AgmtdztH)(dppe)(NO)] (), where xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and dppe = 1,2-bis(diphenylphosphino)ethane, and the assessment of their in vitro antibacterial and anti-cancer efficiency. Among them, diphosphine-containing compounds and were found to exhibit broad-spectrum antibacterial activity characteristics against both Gram-(+) and Gram-(-) bacterial strains, showing high in vitro bioactivity with IC values as low as 4.6 μΜ. In vitro cytotoxicity studies against human ovarian, pancreatic, lung, and prostate cancer cell lines revealed the strong cytotoxic potential of and , with IC values in the range of 3.1-24.0 μΜ, while and maintained the normal fibroblast cells' viability at relatively higher levels. Assessment of these results, in combination with those obtained for analogous Ag(I) complexes bearing similar heterocyclic thioamides, suggest the pivotal role of the substituent groups of the thioamide heterocyclic ring in the antibacterial and anti-cancer efficacy of the respective Ag(I) complexes. Compounds - exhibited moderate in vitro antioxidant capacity for free radicals scavenging, as well as reasonably strong ability to interact with calf-thymus DNA, suggesting the likely implication of these properties in their bioactivity mechanisms. Complementary insights into the possible mechanism of their anti-cancer activity were provided by molecular docking calculations, exploring their ability to bind to the overexpressed fibroblast growth factor receptor 1 (FGFR1), affecting cancer cells' functionalities.
Ag（I）配合物作为抗增殖和抗菌剂，对广泛的癌细胞系和病原体具有抗增殖和抗菌作用，最近引起了人们的极大关注。这些配合物的生物活性潜力取决于它们的结构特征和配体的性质。在此，我们介绍了一系列带有取代的噻二唑基硫代酰胺 5-甲基-1,3,4-噻二唑-2-硫醇（mtdztH）和膦配体的四个 Ag（I）配合物，即 [AgCl（mtdztH）（PPh）]（），[Ag（mtdzt）（PPh）]（），[AgCl（mtdztH）（xantphos）]（）和 [AgmtdztH）（dppe）（NO）]（），其中 xantphos = 4,5-双（二苯基膦基）-9,9-二甲基氧杂蒽和 dppe = 1,2-双（二苯基膦基）乙烷，并评估了它们的体外抗菌和抗癌效率。其中，含二膦的化合物和对革兰氏阳性和革兰氏阴性细菌菌株均表现出广谱的抗菌活性特征，具有低至 4.6 μΜ 的高体外生物活性。对人卵巢、胰腺、肺和前列腺癌细胞系的体外细胞毒性研究表明，化合物和具有很强的细胞毒性潜力，IC 值范围为 3.1-24.0 μΜ，而化合物和保持相对较高水平的正常成纤维细胞活力。这些结果的评估，结合具有类似杂环硫代酰胺的类似 Ag（I）配合物的结果，表明硫代酰胺杂环的取代基在各自 Ag（I）配合物的抗菌和抗癌功效中起着关键作用。化合物-对自由基具有中等的体外抗氧化能力，具有合理的与小牛胸腺 DNA 相互作用的能力，表明这些特性可能与其生物活性机制有关。通过分子对接计算，对其抗癌活性的可能机制提供了补充见解，探索了它们与过度表达的成纤维细胞生长因子受体 1（FGFR1）结合的能力，从而影响癌细胞的功能。
