Optimization Of Drug-like Based On EGFR And ADME/T Characteristics Analysis Of Sesquiterpene

The related parameters of the common drug that treated the non-small cell lung cancer (NSCLC) were calculated, and the pharmacophore features of the drug molecule which target was epidermal growth factor receptor (EGFR) was concluded. On the basis of Gefitinib structure, the new drugs were designed by combinatorial chemistry principles. The drug molecules with high libdock score were obtained through the virtual screening, and then the molecules were predicted and simulated. The research showed that:(1) two kinds of drugs were better than Gefitinib in pharmacokinetics and toxicity,(2) and the molecular dynamic process was as stable as Gefitinib. In order to decrease the clinical side effects of Gefinitib, and to obtain the optional structure of new molecules, the structure of Gefinitib was firstly optimized based on the analyzing result of hydrophobic rings distribution in the active site. Secondly, based on a small molecule library, the Gefinitib structure and the pharmacophore were optimized(1) and obtained 34 optimized structures.(2) Finally, 3 drug molecules that have better indicators and less drug toxicity than Gefinitib were screened based on the calculations of molecular docking, pharmacokinetics, toxicity prediction.To provide quantitative criterion for clinical application, pharmacokinetic and toxic character of 31 kinds of sesquiterpene with bioactivity were analyzed. Pharmacokinetic and toxicity indicators were calculated and analyzed by software. Among 31 kinds of molecules,(1) 13 molecules may do harm to liver,(2) 14 molecules have strong carcinogenicity,(3) 5 molecules cause mutations easily,(4) 10 molecules can not be screened as lead compounds,(5) and only 1 molecule has excellent indicators.31 kinds of sesquiterpenes were classified through index calculation, and the quantized data of pharmacokinetics and toxicity were provided for further clinical experiment.