Binding Model Construction of Antifungal 2-Aryl-4-chromanones Using CoMFA, CoMSIA, and QSAR Analyses

• Published in: Journal of agricultural and food chemistry 2005-03, Vol.53 (5), p.1604-1611
• Main Authors: Wei, Deng-Guo, Yang, Guang-Fu, Wan, Jian, Zhan, Chang-Guo
• Format: Article
• Language: English
• Subjects: 2-aryl-chromanones; Agronomy. Soil science and plant productions; Anthraquinones - chemistry; antifungal properties; Ascomycota - drug effects; binding capacity; Biological and medical sciences; Chemical constitution; chemical structure; Chromones; comparative molecular field analysis; comparative molecular similarity indices analysis; defense mechanisms; Economic plant physiology; Flavanones - chemistry; flavonoids; Fundamental and applied biological sciences. Psychology; fungal diseases of plants; Fungicides, Industrial - chemistry; Fungicides, Industrial - pharmacology; heterocyclic oxygen compounds; Magnaporthe grisea; Models, Molecular; Plant Extracts - chemical synthesis; Plant Extracts - chemistry; Plant Extracts - pharmacology; Quantitative Structure-Activity Relationship; quantitative structure-activity relationships; Sesquiterpenes; Static Electricity; Terpenes
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf048313r

Flavonoids, generated by plants upon attack by a range of pathogens, are demonstrated to have a role in biotic and abiotic stress response phenomena in plants, and there is increasing evidence for the antibacterial, antifungal, and antiviral activities of these compounds. Using the bioisosterism strategy, a series of 2-aryl-4-chromanone derivatives based upon the structure of flavanones, a kind of flavonoid phytoalexins, were synthesized and tested for the antifungal activity against Pyricularia grisea, which have been reported in our previous papers. To further explore the comprehensive structure−activity relationship and construct the binding model for the antifungal compounds, two kinds of molecular field analysis techniques, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), were performed following a Hansch−Fujita QSAR study. Superimpositions were performed using three alignment rules, that is, centroid-based alignment, common substructure-based alignment, and field fit alignment, and statistically reliable models with good predictive power (CoMFA r 2 = 0.952, q 2 = 0.727; CoMSIA r 2 = 0.965, q 2 = 0.751) were achieved on the basis of the common substructure-based alignment. The combined results of CoMFA, CoMSIA, and former Hansch−Fujita QSAR analyses resulted in comprehensive understanding about the structure−activity relationships, which led to this construction of a plausible binding model of the title compounds. Keywords: CoMFA; CoMSIA; Hansch−Fujita QSAR; 2-aryl-4-chromanones derivatives; binding model