Synthesis and in vitro antifungal activities of new 3-substituted benzopyrone derivatives.
A series of new benzopyrone compounds were designed and synthesized and their antifungal activities in vitro were evaluated. The results showed that the benzopyrone derivatives with short terminal alkyl chain exhibited potent antifungal activity, which represent a novel class of promising leads for the development of novel non-azole antifungal agents. Compound 5j is the most potent one with MIC(80) value 1.5 μg/mL against Trichophyton rubrum. Flexible molecular docking was used to analyze the structure-activity relationships (SARs) of the compounds. The designed compounds interact with CA-CYP51 through hydrophobic and van der Waals interactions.
Lv
Zhiliang
Z
Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, China.
Sheng
Chunquan
C
Zhang
Yikai
Y
Wang
Tiantian
T
Feng
Jilu
J
Sun
Hailing
H
Zhong
Hanyu
H
Zhang
Mingfeng
M
Chen
Huan
H
Li
Ke
K
D058888:14-alpha Demethylase Inhibitors; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D003198:Computer Simulation; D015195:Drug Design; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D011485:Protein Binding; D011753:Pyrones / Q000138:chemical synthesis* / Q000494:pharmacology; D058886:Sterol 14-Demethylase / Q000187:drug effects; D013329:Structure-Activity Relationship; D014249:Trichophyton / Q000187:drug effects*
D058888:14-alpha Demethylase Inhibitors; D000935:Antifungal Agents; D001578:Benzopyrans; D011753:Pyrones; D058886:Sterol 14-Demethylase