Toxicity remission of PAEs on multireceptors after molecular modification through a 3D-QSAR pharmacophore model coupled with a gray interconnect degree method

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.

___

  • Babu-Rajendran R, 2018, J CHROMATOGR B, V1079, P15, DOI 10.1016/j.jchromb.2018.01.039
  • Bao HJ, 2008, CHINESE MED BIOTECHN, V3, P266
  • Bie Cong-cong, 2012, Huanjing Kexue, V33, P442
  • Bope A, 2019, ENVIRON SCI-PROC IMP, V21, P1268, DOI 10.1039/c9em00050j
  • Chen B., 2009, THESIS TIANJIN U TIA, DOI [10.7666/d.y1677265, DOI 10.7666/D.Y1677265]
  • Chen ZF, 2006, CHINESE J HLTH LAB T, V16, P772
  • [崔杰 CUI Jie], 2008, [中国管理科学, Chinese Journal of Management Science], V16, P141
  • Diller DJ, 2001, PROTEINS, V43, P113, DOI 10.1002/1097-0134(20010501)43:2<113::AID-PROT1023>3.0.CO;2-T
  • Elcombe CR, 2002, ENVIRON HEALTH PERSP, V110, P363, DOI 10.1289/ehp.02110363
  • Ema M, 1996, TOXICOL LETT, V86, P19 .
  • Fromme H, 2004, INDOOR AIR, V14, P188, DOI 10.1111/j.1600-0668.2004.00223.x
  • Gao ZP, 2017, JIANGSU AGR SCI, V45, P155, DOI [10.15889/j.issn.1002-1302.2017.17.042, DOI 10.15889/J.ISSN.1002-1302.2017.17.042]
  • [葛建 Ge Jian], 2011, [海洋与湖沼, Oceanologia et Limnologia Sinica], V42, P549
  • GIAM CS, 1978, SCIENCE, V199, P419, DOI 10.1126/science.413194
  • Hu X., 2003, CHINESE J HLTH LAB T, V13, P9
  • Huang H.-J., 2014, EVID-BASED COMPL ALT, V2014
  • Jiang L., 2016, INVESTIGATION IDENTI .
  • Jiang L, 2016, J HAZARD MATER, V307, P202, DOI 10.1016/j.jhazmat.2015.12.031
  • Jin DC, 2013, INT J MOL SCI, V14, P24046, DOI 10.3390/ijms141224046
  • Lapinskas PJ, 2005, TOXICOLOGY, V207, P149, DOI 10.1016/j.tox.2004.09.008
  • LEE RF, 1971, MAR BIOL, V9, P99, DOI 10.1007/BF00348249
  • LEPAGE G, 1991, ANAL BIOCHEM, V197, P277, DOI 10.1016/0003-2697(91)90392-7
  • [李海涛 Li Haitao], 2006, [环境污染与防治, Environmental Pollution & Control], V28, P853
  • Li HN, 2010, CHEMOSPHERE, V80, P845, DOI 10.1016/j.chemosphere.2010.06.006
  • Liu GH, 2017, J SEP SCI, V40, P2603, DOI 10.1002/jssc.201601428
  • Lo Re V III, 2002, ANN INTERN MED, V136, P634, DOI 10.7326/0003-4819-136-8-200204160-00022
  • Melchers WJG, 1997, J VIROL, V71, P686, DOI 10.1128/JVI.71.1.686-696.1997
  • MURRAY AP, 1991, MAR POLLUT BULL, V22, P595, DOI 10.1016/0025-326X(91)90247-P
  • Nayana RS, 2009, J CHEM INF MODEL, V49, P53, DOI 10.1021/ci800294y
  • Net S, 2015, ENVIRON SCI TECHNOL, V49, P4019, DOI 10.1021/es505233b
  • Organization for Economic Co-operation and Development (OECD), 2007, OECD SER OIL TEST AS
  • Patyna P, 2000, MAR ENVIRON RES, V50, P194
  • Qian HF, 2009, CHEMOSPHERE, V75, P368, DOI 10.1016/j.chemosphere.2008.12.040
  • Qiu YL, 2018, SPECTROSC SPECT ANAL, V38, P441, DOI 10.3964/j.issn.1000-0593(2018)02-0441-07
  • Qiu YL, 2018, SPECTROSC LETT, V51, P155, DOI 10.1080/00387010.2018.1442353
  • Selvaraj KK, 2015, ENVIRON GEOCHEM HLTH, V37, P83, DOI 10.1007/s10653-014-9632-5
  • Song WH, 2011, ENVIRON TOXICOL PHAR, V32, P102, DOI 10.1016/j.etap.2011.04.001
  • Staples CA, 1997, CHEMOSPHERE, V35, P667, DOI 10.1016/S0045-6535(97)00195-1
  • Suzuki T, 2001, ENVIRON SCI TECHNOL, V35, P3757, DOI 10.1021/es001860i
  • Wang T, 2012, ENVIRON TOXICOL PHAR, V34, P59, DOI 10.1016/j.etap.2012.02.008
  • Wang XL, 2017, ENVIRON SCI POLLUT R, V24, P25114, DOI 10.1007/s11356-017-0129-5
  • Watanabe T, 2001, B ENVIRON CONTAM TOX, V66, P456
  • [魏杰 Wei Jie], 2019, [大连海洋大学学报, Journal of Dalian Ocean University], V34, P1
  • Wu ZH, 2006, THESIS JINAN U GUANG .
  • Xie XL, 2010, INVESTIGATIONS REGUL .
  • Xin ML, 2018, CHEM J CHINESE U, V39, P299, DOI 10.7503/cjcu20170402
  • Zhang LL, 2015, ECOTOXICOLOGY, V24, P967, DOI 10.1007/s10646-015-1446-4
  • Zhang Shaoliang, 1996, SYSTEMS ENG, V14, P45
  • Zhang YC, 2015, THESIS ZHEJIANG SCI, DOI [10.7666/d.D630788, DOI 10.7666/D.D630788]
  • Zhang YC, 2017, J ZHEJIANG OCEAN U N, V36, P360, DOI [10.3969/j.issn.1008-830X.2017.04.013, DOI 10.3969/J.ISSN.1008-830X.2017.04.013]
  • Zhao YY, 2019, J CLEAN PROD, V221, P113, DOI 10.1016/j.jclepro.2019.02.156
  • ZHOU JJ, 2012, CHEM ENG, V5, P24 .
  • Zou Yadan, 2017, Asian Journal of Ecotoxicology, V12, P25, DOI 10.7524/AJE.1673-5897.20170518001