Siebert Agnieszka, Wysocka Magdalena, Krawczyk Beata, Cholewiński Grzegorz, Rachoń Janusz
Department of Organic Chemistry, Gdansk University of Technology, ul. G. Narutowicza 11/12, 80-233 Gdansk, Poland.
Department of Molecular Biotechnology and Microbiology, Gdansk University of Technology, ul. G. Narutowicza 11/12, 80-233 Gdansk, Poland.
Eur J Med Chem. 2018 Jan 1;143:646-655. doi: 10.1016/j.ejmech.2017.11.094. Epub 2017 Dec 1.
The series of 16 novel amino acid and peptide mycophenolic acid (MPA) derivatives was obtained as potential antibacterial agents. Coupling of MPA with respective amines was optimized with condensing reagents such as EDCI/DMAP and T3P/TEA. Amino acid analogs were received both as methyl esters and also with the free carboxylic group. The biological activity of the products was tested on five references bacterial strains: Klebsiella pneumoniae ATCC 700603 (ESBL), Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus MRSA ATCC 43300, Staphylococcus aureus MSSA ATCC 25923. Peptide derivatives proved to be the most versatile ones, their MIC values relative to most strains was lower than MPA alone. It has been noted that the activity of amino acid derivatives depends on the configuration at the chiral center in the amino acid unit and methyl esters indicated better antimicrobial activity than analogs with free carboxylic group.
获得了一系列16种新型氨基酸和肽类霉酚酸（MPA）衍生物作为潜在的抗菌剂。使用诸如EDCI/DMAP和T3P/TEA等缩合试剂优化了MPA与相应胺的偶联。氨基酸类似物以甲酯形式以及带有游离羧基的形式获得。在五种参考细菌菌株上测试了产物的生物活性：肺炎克雷伯菌ATCC 700603（产超广谱β-内酰胺酶）、大肠埃希菌ATCC 8739、铜绿假单胞菌ATCC 27853、金黄色葡萄球菌MRSA ATCC 43300、金黄色葡萄球菌MSSA ATCC 25923。肽衍生物被证明是最具通用性的，它们相对于大多数菌株的最低抑菌浓度（MIC）值低于单独的MPA。已经注意到氨基酸衍生物的活性取决于氨基酸单元手性中心的构型，并且甲酯显示出比带有游离羧基的类似物更好的抗菌活性。
