Synthesis and antibacterial activity evaluation of octapeptin derivatives

VernacularTitle:八肽菌素衍生物的合成及其抗菌活性研究
Author: He-xian YANG ; A-long CUI ; Yong-jian WANG ; Shi-bo KOU ; Miao LÜ ; Hong YI ; Zhuo-rong LI
Publication Type:Research Article
Keywords: bacterial resistance; octapeptin; structural modification; broad-spectrum antibacterial activity
From: Acta Pharmaceutica Sinica 2024;59(1):152-160
CountryChina
Language:Chinese
Abstract: Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.