Synthesis and QSAR study of novel α-methylene-γ-butyrolactone derivatives as antifungal agents.
Thirty-six new α-benzylidene-γ-lactone compounds based α-methylene-γ-butyrolactone substructure were prepared and characterized by spectroscopic analysis. All compounds were evaluated for antifungal activities in vitro against six plant pathogenic fungi and the half maximal inhibitory concentration (IC50) against Botrytis cinerea and Colletotrichum lagenarium were investigated. Compounds 5c-3 and 5c-5 with the halogen atom exhibited excellent fungicidal activity against B. cinerea (IC50=22.91, 18.89μM). The structure-activity relationships (SARs) analysis indicated that the derivatives with electron-withdrawing substituents at the meta- or para-positions improves the activity. Via the heuristic method, the generated quantitative structure-activity relationship (QSAR) model (R2=0.961) revealed a strong correlation of antifungal activity against B. cinerea with molecular structures of these compounds. Meanwhile, the cytotoxicity of 20 representative derivatives was tested in the human tumor cells line (HepG2) and the hepatic L02 cells line, the result indicated that the synthesized compounds showed significant inhibitory activity and limited selectivity. Compound 5c-5 has the highest fungicidal activity with IC50=18.89μM (against B. cinerea.) but low cytotoxicity with IC50=35.4μM (against HepG2 cell line) and IC50=68.8μM (against Hepatic L02 cell line). These encouraging results can be providing an alternative, promising use of α-benzylidene-γ-lactone through the design and exploration of eco-friendly fungicides with low toxicity and high efficiency.
Research and Development Center of Biorational Pesticide, Northwest A&F University, Yangling 712100, Shaanxi, China.
Yong-Ling
YL
Wu
Research and Development Center of Biorational Pesticide, Northwest A&F University, Yangling 712100, Shaanxi, China.
De-Long
DL
Wang
Research and Development Center of Biorational Pesticide, Northwest A&F University, Yangling 712100, Shaanxi, China.
En-Hui
EH
Guo
Research and Development Center of Biorational Pesticide, Northwest A&F University, Yangling 712100, Shaanxi, China.
Shuang
S
Song
Research and Development Center of Biorational Pesticide, Northwest A&F University, Yangling 712100, Shaanxi, China; Engineering and Research Center of Biological Pesticide of Shaanxi Province, Yangling 712100, Shaanxi, China. Electronic address: fengjt@nwsuaf.edu.cn.
Jun-Tao
JT
Feng
Research and Development Center of Biorational Pesticide, Northwest A&F University, Yangling 712100, Shaanxi, China; Engineering and Research Center of Biological Pesticide of Shaanxi Province, Yangling 712100, Shaanxi, China.
Xing
X
Zhang
D015107:4-Butyrolactone / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005658:Fungi / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D021281:Quantitative Structure-Activity Relationship
D000935:Antifungal Agents; D015107:4-Butyrolactone
Antifungal activity; Cytotoxicity; Heuristic method; QSAR; α-benzylidene-γ-lactone derivatives