化学
立体化学
抗菌活性
对接(动物)
糖苷
细菌
生物化学
组合化学
遗传学
医学
生物
护理部
作者
Alexander Dreger,Katharina J. Hoff,Oriana Agoglitta,Emre F. Bülbül,Jelena Melesina,Wolfgang Sippl,Ralph Holl
标识
DOI:10.1016/j.bioorg.2021.105403
摘要
The bacterial deacetylase LpxC is a promising target for the development of novel antibiotics being selectively active against Gram-negative bacteria. In chiral pool syntheses starting from d- and l-ribose, a series regio- and stereoisomeric monohydroxytetrahydrofuran derivatives was synthesized and tested for LpxC inhibitory and antibacterial activities. Molecular docking studies were performed to rationalize the obtained structure-activity relationships. The (2S,3R,5R)-configured 3-hydroxytetrahydrofuran derivative ent-8 ((2S,3R,5R)-N,3-Dihydroxy-5-(4-{[4-(morpholinomethyl)phenyl]ethynyl}phenyl)tetrahydrofuran-2-carboxamide) was found to be the most potent LpxC inhibitor (Ki = 3.5 µM) of the synthesized series of monohydroxytetrahydrofuran derivatives and to exhibit the highest antibacterial activity against E. coli BL21(DE3) and the D22 strain.
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