In Silico Predictions of Endocrine Disruptors Properties

Abstract

Endocrine-disrupting chemicals (EDCs) are a broad class of molecules present in our environment that are suspected to cause adverse effects in the endocrine system by interfering with the synthesis, transport, degradation, or action of endogenous ligands. The characterization of the harmful interaction between environmental compounds and their potential cellular targets and the development of robust in vivo, in vitro, and in silico screening methods are important for assessment of the toxic potential of large numbers of chemicals. In this context, computer-aided technologies that will allow for activity prediction of endocrine disruptors and environmental risk assessments are being developed. These technologies must be able to cope with diverse data and connect chemistry at the atomic level with the biological activity at the cellular, organ, and organism levels. Quantitative structure–activity relationship methods became popular for toxicity issues. They correlate the chemical structure of compounds with biological activity through a number of molecular descriptors (e.g., molecular weight and parameters to account for hydrophobicity, topology, or electronic properties). Chemical structure analysis is a first step; however, modeling intermolecular interactions and cellular behavior will also be essential. The increasing number of three-dimensional crystal structures of EDCs’ targets has provided a wealth of structural information that can be used to predict their interactions with EDCs using docking and scoring procedures. In the present review, we have described the various computer-assisted approaches that use ligands and targets properties to predict endocrine disruptor activities.

Piperazine-substituted derivatives of favipiravir for Nipah virus inhibition: What do in silico studies unravel?

“…The GI absorption was studied, and the molecules had a high absorption, making it potential leads for drug discovery. In silico toxicity analysis is evolving as a platform for predicting the toxic effects of chemicals on humans, animals, and the environment [68][69][70]. Molecules were analysed for carcinogenicity, immunotoxicity, mutagenicity, and cytotoxicity, which are classified as toxicological endpoints in the Pro Tox II webserver.…”

Human Health Consequences of Endocrine-Disrupting Chemicals

“…The experimental screening process of the EDCs using animal data is timeconsuming and costly. Computer-based (in silico) methods have been developed to predict the effect of the EDCs on the endocrine receptor [5,49]. One popular method is the molecular docking approach.…”

“…The number of EDCs has markedly increased over the past 60 years. Humans are constantly exposed to hundreds of EDCs mainly through air, water, and food [1][2][3][4][5][6][7][8][9].…”

The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds

“…As reviewed in Schneider et al [22], the majority of in silico studies for identifying potential MDCs and studying NR mediated interactions involved in metabolic disorder apply (Q)SAR models. Further, physiologically-based toxicokinetic/pharmacokinetic (PBTK/PBPK) models have been used for prediction of absorption, distribution, metabolism, and excretion (ADME) processes and facilitation of quantitative in vitro-in vivo extrapolation (QIVIVE).…”