Cho Hyunjoo, Chung Beomkoo, Kim Chang-Kwon, Oh Dong-Chan, Oh Ki-Bong, Shin Jongheon
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, 151-742, Korea.
Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, 151-921, Korea.
Arch Pharm Res. 2017 Apr;40(4):518-523. doi: 10.1007/s12272-016-0884-8. Epub 2017 Jan 18.
Sortases are a family of Gram-positive transpeptidases responsible for anchoring surface protein virulence factors to the peptidoglycan cell wall layer. In Staphylococcus aureus (S. aureus), deletion of sortase isoform results in a significant reduction in virulence and infection potential. Twenty flavonoids were isolated from the stem of the folk medicinal plant Spatholobus suberectus Dunn. These compounds were tested against S. aureus-derived sortase A (SrtA), a key transpeptidase for bacterial virulence. Among these active flavonoids, 7-hydroxy-6-methoxy-flavanone (3) and formononetin (10) were identified as compounds with promising SrtA inhibitory activity. These compounds also exhibited inhibitory activity against S. aureus cell clumping to fibrinogen. The suppression of cell-clumping activity indicates the potential of these compounds in the treatment of S. aureus infections via the inhibition of SrtA.
分选酶是一类革兰氏阳性转肽酶，负责将表面蛋白毒力因子锚定到肽聚糖细胞壁层。在金黄色葡萄球菌中，分选酶同工型的缺失会导致毒力和感染潜力显著降低。从民间药用植物密花豆的茎中分离出20种黄酮类化合物。这些化合物针对金黄色葡萄球菌衍生的分选酶A（SrtA）进行了测试，SrtA是细菌毒力的关键转肽酶。在这些活性黄酮类化合物中，7-羟基-6-甲氧基黄酮（3）和刺芒柄花素（10）被鉴定为具有良好SrtA抑制活性的化合物。这些化合物还表现出对金黄色葡萄球菌细胞与纤维蛋白原聚集的抑制活性。细胞聚集活性的抑制表明这些化合物通过抑制SrtA在治疗金黄色葡萄球菌感染方面的潜力。
