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Computer-aided drug discovery: Novel 3,9-disubstituted eudistomin U derivatives as potent antibacterial agents
Jiangkun Dai1, Wenjia Dan1, Na Li1
1College of Chemistry & Pharmacy, Northwest A&F University, 22 Xinong Road, Yangling, 712100, Shaanxi, China.
Abstract:
Thirty-two new 3,9-disubstituted eudistomin U derivatives were designed and synthesized based on computer-aided drug discovery (CADD). Sixteen 3,9-disubstituted eudistomin U derivatives (6a-6p) have exhibited potent antibacterial activity. Specially, the most active compound 6p displayed better activity than commercial drugs fosfomycin sodium, ciprofloxacin and propineb, with a peak minimum inhibitory concentration (MIC) of 1.5625 μmol/L. The antibacterial mechanism indicated that these compounds could exert bactericidal effect by damaging bacterial cell membrane and disrupting the function of DNA gyrase.
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