1. Synthesis and Antibacterial Evaluation of Novel 3-Substituted Ocotillol-Type Derivatives as Leads.
- Author
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Yi Bi, Xian-Xuan Liu, Heng-Yuan Zhang, Xiao Yang, Ze-Yun Liu, Jing Lu, Lewis, Peter John, Chong-Zhi Wang, Jin-Yi Xu, Qing-Guo Meng, Cong Ma, and Chun-Su Yuan
- Subjects
BACTERIAL disease treatment ,GRAM-positive bacteria ,ANTIBIOTICS assay ,AMINO acid analysis ,KANAMYCIN - Abstract
Due to the rapidly growing bacterial antibiotic-resistance and the scarcity of novel agents in development bacterial infection is still a global problem. Therefore, new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. In this paper, a series of antibacterial ocotillol-type C-24 epimers modified from natural 20(S)-protopanaxadiol were synthesized and evaluated for their antibacterial activity. According to the screening results of Gram-positive bacteria (B. subtilis 168 and MRSA USA300) and Gram-negative bacteria (P. aer PAO1 and A. baum ATCC19606) in vitro, the derivatives exhibited good antibacterial activity, particularly against Gram-positive bacteria with an minimum inhibitory concentrations (MIC) value of 2-16 μg/mL. The subsequent synergistic antibacterial assay showed that derivatives 5c and 6c enhanced the susceptibility of B. subtilis 168 and MRSA USA300 to chloramphenicol (CHL) and kanamycin (KAN) (FICI < 0.5). Our data showed that ocotillol-type derivatives with long-chain amino acid substituents at C-3 were good leads against antibiotic-resistant pathogens MRSA USA300, which could improve the ability of KAN and CHL to exhibit antibacterial activity at much lower concentrations with reduced toxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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