Antoszczak Michał, Maj Ewa, Napiórkowska Agnieszka, Stefańska Joanna, Augustynowicz-Kopeć Ewa, Wietrzyk Joanna, Janczak Jan, Brzezinski Bogumil, Huczyński Adam
Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89 b, 61-614 Poznań, Poland.
Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland.
Molecules. 2014 Nov 25;19(12):19435-59. doi: 10.3390/molecules191219435.
A series of 12 novel monosubstituted N-benzyl amides of salinomycin (SAL) was synthesized for the first time and characterized by NMR and FT-IR spectroscopic methods. Molecular structures of three salinomycin derivatives in the solid state were determined using single crystal X-ray method. All compounds obtained were screened for their antiproliferative activity against various human cancer cell lines as well as against the most problematic bacteria strains such as methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), and Mycobacterium tuberculosis. Novel salinomycin derivatives exhibited potent anticancer activity against drug-resistant cell lines. Additionally, two N-benzyl amides of salinomycin revealed interesting antibacterial activity. The most active were N-benzyl amides of SAL substituted at -ortho position and the least anticancer active derivatives were those substituted at the -para position.
首次合成了一系列12种新型单取代盐霉素（SAL）的N-苄基酰胺，并通过核磁共振（NMR）和傅里叶变换红外光谱（FT-IR）方法对其进行了表征。采用单晶X射线法测定了三种盐霉素衍生物的固态分子结构。对所获得的所有化合物进行了筛选，以检测它们对各种人类癌细胞系以及对最具问题的细菌菌株（如耐甲氧西林金黄色葡萄球菌（MRSA）、表皮葡萄球菌（MRSE）和结核分枝杆菌）的抗增殖活性。新型盐霉素衍生物对耐药细胞系表现出强大的抗癌活性。此外，两种盐霉素的N-苄基酰胺显示出有趣的抗菌活性。活性最高的是在邻位取代的SAL的N-苄基酰胺，而抗癌活性最低的衍生物是在对位取代的那些。
