Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Poznan, Poland.
Medical University of Warsaw, Department of Pharmaceutical Microbiology, Oczki 3, 02-007 Warsaw, Poland.
Eur J Med Chem. 2014 Apr 9;76:435-44. doi: 10.1016/j.ejmech.2014.02.031. Epub 2014 Feb 14.
A series of 12 novel ester derivatives of naturally occurring polyether antibiotic - salinomycin were synthesized, characterised by spectroscopic method and evaluated for their in vitro antibacterial activity and cytotoxicity. The new esters were demonstrated to form complexes with monovalent and divalent metal cation of 1:1 stoichiometry in contrast to the salinomycin which forms only complexes with monovalent cations. All the obtained compounds show potent antiproliferative activity against human cancer cell lines and a good selectivity index for cancer versus mammalian cells. Additionally, 3 compounds showed higher antiproliferative activity against the drug-resistant cancer cells and lower toxicity towards normal cells than those of unmodified salinomycin and standard anticancer drugs such as cisplatin and doxorubicin. Some of the synthesized compounds showed good inhibitory activity against Staphylococcus strains and clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE). These studies show that salinomycin esters are interesting scaffolds for the development of novel anticancer and Gram-positive antibacterial agents.
合成了一系列 12 种新型酯衍生物天然多醚抗生素 - 盐霉素，通过光谱方法进行了表征，并评估了它们的体外抗菌活性和细胞毒性。与仅与单价阳离子形成配合物的盐霉素相反，这些新酯被证明可以与单价和二价金属阳离子以 1:1 的化学计量比形成配合物。所有获得的化合物对人癌细胞系表现出很强的抗增殖活性，对癌细胞与哺乳动物细胞的选择性指数良好。此外，与未修饰的盐霉素和顺铂、阿霉素等标准抗癌药物相比，3 种化合物对耐药癌细胞的抗增殖活性更高，对正常细胞的毒性更低。一些合成化合物对金黄色葡萄球菌株和耐甲氧西林金黄色葡萄球菌（MRSA）和表皮葡萄球菌（MRSE）的临床分离株表现出良好的抑制活性。这些研究表明，盐霉素酯是开发新型抗癌和革兰氏阳性抗菌剂的有趣支架。
