A study of possible substitutes for the endocrine disruptor DEHP in two hormone receptors

Author(s)

Almeida, Michell O. ^[1] ; Lanza, Marcos R. V. ^[1] ; Honorio, Kathia M. ^{[2, 3]}

Affiliation

^[1] Univ Sao Paulo, Sao Carlos Inst Chem, Sao Carlos, SP - Brazil

^[2] Univ Sao Paulo, Sch Arts Sci & Humanities, Sao Paulo - Brazil

^[3] Fed Univ ABC, Ctr Nat Sci & Humanities, Santo Andre, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS; AUG 2021.
• Web of Science Citations: 0

Abstract

Bis(2-ethylhexyl) phthalate (DEHP) has been widely used for the production of plastics, and the compound has also been found to act as endocrine disruptor. Exposure to DEHP has been found to cause several hormonal problems, including decreased fertility. Due to the environmental and health risks posed by the use of DEHP, the present study employed molecular docking, molecular dynamics, and free energy analyses (MM-GBSA, MM-PBSA, and SIE) aiming at evaluating the action of DEHP and that of two other compounds (ATEC and DL9TH), tested as potential DEHP substitutes, on two hormone receptors (sex hormone-binding globulin - SHBG - and progesterone receptor - PR). The results obtained showed that ATEC may be a good substitute for DEHP in the production of plastics, such as PVC, considering that the compound recorded the greatest free energy values with respect to binding with SHBG (-31.36 kcal/mol obtained from MM-GBSA; -20.28 kcal/mol for MM-PBSA, and -7.40 for SIE) and PR (-36.40 kcal/mol for MM-GBSA; -27.00 kcal/mol for MM-PBSA, and -8.51 kcal/mol for SIE) - this shows that ATEC presented the least activity in the two hormone receptors. The findings of this study provide relevant insights on potential substitutes for DEHP and help shed light on the action of these new efficient substances, which have similar properties to DEHP (ATEC and DL9TH) yet do not act as endocrine disruptors. Communicated by Ramaswamy H. Sarma (AU)

• FAPESP's process: 17/10118-0 - Study and application of electrochemical technology for the analysis and degradation of endocrine interferents: materials, sensors, processes and scientific dissemination
• Grantee: Marcos Roberto de Vasconcelos Lanza
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/19103-8 - Computational Study of Electrochemical Properties Related to the Degradation of Endocrine Disruptors
• Grantee: Michell de Oliveira Almeida
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/50945-4 - INCT 2014: National Institute for Alternative Technologies of Detection, Toxicological Evaluation and Removal of Micropollutants and Radioactivies
• Grantee: Maria Valnice Boldrin
• Support Opportunities: Research Projects - Thematic Grants