QSAR And Its Application In Molecular Design Of Novel Pesticides

Quantitative structure-activity relationship (QSAR) studies are important approaches in the design of pesticidal molecules; the method of Hansch-Fujita QSAR of 2D-QSAR, comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA) are been introduced in detail in this paper, and the different types of descriptors of Hansch-Fujita QSAR are been compared and discussed. Based on three methods above, two kinds of studies are been carried out.To further explore the comprehensive structure-activity relationship of the antifungal 2-Aryl-4- chromanones, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), are performed to explore the structure-activity relationship of the antifungal 2-Aryl-4- chromanones, based on the result of the Hansch-Fujita QSAR analysis that was performed in our group previously. The compare and the combination with the result of the Hansch-Fujita QSAR analysis provide more comprehensive understand about the relationship between the structure and the activity, and help to construct the binding model between the ligand and the plausible receptor. The binding model provides a helpful guideline for further designing novel potent antifungal agents definitely.The development of sulfoylurea herbicides has always been the important study field in herbicide chemistry nowadays; on one hand, several kinds of receptor action models have been advanced by scientists, based on the character of the structure of sulfonylureas; on the other hand, molecular models and docking models have been constructed according to the information of their target (Acetohydroxyacid synthase [AHAS], EC2.2.1.6). More information about the inhibition mechanism would be gotten if the study is based on the connection of SAR of inhibitors and the property of the binding site of enzyme. For that, according to the crystal structure of yeast AHAS in complex with sulfonylureas that were reported by the group of Duggleby,the geometry of chlorimuron in the crystal structure of yeast AHAS in complex with chlorimuron is extracted as initial structure in this study, which is used to construct a series of sulfonylurea herbicides molecules. All of the constructed structures are fully optimized by using the DFT method with the B3LYP functional, and electrostatic potential (ESP)-fitting charges are derived from the DFT calculation. Then, DFT-based quantum chemical descriptors are used to carry out Hansch-Fujita QSAR analysis, and at the same time, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), are performed to explore the structure-activity relationship of sulfonylurea compounds. The derived QSAR models further validate the binding model of sulfonylurea compounds and AHAS, and provide a very useful tool in the next virtual screening.