Open AccessToxicity remission of PAEs on multireceptors after molecular modification through a 3D-QSAR pharmacophore model coupled with a gray interconnect degree method
Author(s) -
Xinyi Chen,
Yu Liu
Publication year - 2021
Publication title -
turkish journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.239
H-Index - 46
eISSN - 1303-6130
pISSN - 1300-0527
DOI - 10.3906/kim-2008-38
Subject(s) - pharmacophore , chemistry , quantitative structure–activity relationship , toxicity , molecule , derivative (finance) , acute toxicity , computational chemistry , stereochemistry , combinatorial chemistry , organic chemistry , financial economics , economics
In the proposed model, the gray interconnect degree method was employed to process the acute toxicity values of phthalate acid esters (PAEs) to green algae, daphnia, mysid, and fish (predicted by EPI Suite software) and to obtain the comprehensive characterization value of the multireceptor toxicity effect (MTE) of PAEs. The 3D-QSAR pharmacophore model indicated that hydrophobic groups significantly affected the MTE of PAEs. Based on this, 16 PAEs derivative molecules with significantly decreased comprehensive characterization value (more than 10%) of the toxic effects of multireceptors were designed. Among them, 13 PAEs derivative molecules reduced the toxicity values (predicted by the EPI Suite software) of four receptor organisms to varying degrees. Finally, two derivative molecules from PAEs were screened and could exist stably in the environment. The derivative molecule's reduced toxicity to the receptor was obtained through molecular docking methods and simulated the PAEs' primary metabolic response pathways. The above research results break through the pharmacophore model's limitation of only being suitable for the single effect of pollutants. Its application provides a new theoretical verification basis for expanding the multieffect pharmacophore model.