Molecular Modification of Benzophenone Derivatives for Lower Bioenrichment and Toxicity Through the Pharmacophore Model  

作　　者：XIAO Jiapeng ZHANG Wenhui ZHANG Shujing LI Yu 

机构地区：[1]College of Environmental Science and Engineering,North China Electric Power University,Beijing 102206,P.R.China [2]Key Laboratory of Resource and Environmental System Optimization,Ministry of Education,North China Electric Power University,Beijing 102206,P.R.China

出　　处：《Chemical Research in Chinese Universities》2022年第2期535-545,共11页高等学校化学研究（英文版）

摘　　要：In this study,we used the improved extreme-difference normalization method to calculate the comprehensive evaluation values of bioenrichment and toxicity of benzophenone UV light absor-bers(BPs).Based on this parameter,a 3D-QSAR(QSAR=quantitative structure activity relationship)pharmacophore model was constructed using Discovery Studio software and applied to the mole-cular modification of BPs.With three commonly used ingredients in sunscreen 2-hydroxy-4-methoxybenzophenone(BP-3),2,2'-dihydroxy-4,4'-dimethoxybenzophenone(BP-6)and 2,2'-dihydroxy-4-methoxybenzophenone(BP-8)as target molecules,we performed BPs substitution reaction based on the binding positions of characteristic elements of the pharmacophore model and designed BP derivatives with reduced bioenrichment and toxicity.Stability and function evaluation showed that while the stability of 6 BP derivatives was enhanced,the light absorption capacity was also significantly enhanced(from 9.16%to 43.16%).Molecular dynamics simulation results showed that the binding ability of BP-609 molecule with serum albumin was reduced by 16.37%compared with BP-6,and the binding with collagen could not occur spontaneously,which could be used as an explanation for the simultaneous reduction of its bioenrichment and toxicity.Besides,through the simulation of human metabolism,it was found that the liver metabolites of BP-609 were less toxic,which reduced the potential risk of human metabolism.It proved that the molecular modification scheme of BPs was environment-friendly.

关 键 词：Benzophenone type UV absorber Bioenrichment TOXICITY Comprehensive effect evaluation model Molecular modification 

分 类 号：O62[理学—有机化学]