Binding model construction of antifungal 2-aryl-4-chromanones using CoMFA, CoMSIA, and QSAR analyses.
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.
Wei
Deng-Guo
DG
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education of China and College of Chemistry, Central China Normal University, Wuhan 430079, People's Republic of China.
Yang
Guang-Fu
GF
Wan
Jian
J
Zhan
Chang-Guo
CG
D000880:Anthraquinones / Q000737:chemistry*; D001203:Ascomycota / Q000187:drug effects; D002867:Chromones; D044950:Flavanones / Q000737:chemistry; D005659:Fungicides, Industrial / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D010936:Plant Extracts / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D012717:Sesquiterpenes; D055672:Static Electricity; D013729:Terpenes; D000094162:Phytoalexins
D000880:Anthraquinones; D002867:Chromones; D044950:Flavanones; D005659:Fungicides, Industrial; D010936:Plant Extracts; D012717:Sesquiterpenes; D013729:Terpenes; C469373:chaetomanone; D000094162:Phytoalexins