Prediction of ADME-Tox properties and toxicological endpoints of triazole fungicides used for cereals protection

Gridan, Ionut Mădălin; Ciorsac, Alecu; Isvoran, Adriana

doi:10.5599/admet.668

Cited by 18 publications

(27 citation statements)

References 37 publications

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“…The computational tools that are used in this study have been elaborated for assessing the pharmacological profiles and toxicological endpoints of new drugs, but they were successfully applied for other classes of chemicals: cosmetic ingredients and pesticides (Alves et al, 2018c; Roman et al, 2018a; Gridan et al, 2019), synthetic steroids found on the market as food supplements or veterinary drugs (Roman et al, 2018b), water soluble derivatives of chitosan (Isvoran et al, 2017). It illustrates their applicability for predicting pharmacological properties and toxicological endpoints for many classes of compounds.…”

Section: Methodsmentioning

confidence: 99%

Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan

Roman

Som

et al. 2019

Front. Bioeng. Biotechnol.

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Chitosan is a natural polymer revealing an increased potential to be used in different biomedical applications, including drug delivery systems, and tissue engineering. It implies the evaluation of the organism response to the biomaterial implantation. Low-molecular degradation products, the chito-oligomers, are resulting mainly from the influence of enzymes, which are found in the organism fluids. Within this study, we have performed the computational assessment of pharmacological profiles and toxicological effects on human health of small chito-oligomers with distinct molecular weights, deacetylation degrees, and acetylation patterns. Our approach is based on the fact that regulatory agencies and researchers in the drug development field rely on the use of modeling to predict biological effects and to guide decision making. To be considered as valid for regulatory purposes, every model that is used for predictions should be associated with a defined toxicological endpoint and has appropriate robustness and predictivity. Within this context, we have used FAF-Drugs4, SwissADME, and PreADMET tools to predict the oral bioavailability of chito-oligomers and SwissADME, PreADMET, and admetSAR2.0 tools to predict their pharmacokinetic profiles. The organs and genomic toxicities have been assessed using admetSAR2.0 and PreADMET tools but specific computational facilities have been also used for predicting different toxicological endpoints: Pred-Skin for skin sensitization, CarcinoPred-EL for carcinogenicity, Pred-hERG for cardiotoxicity, ENDOCRINE DISRUPTOME for endocrine disruption potential and Toxtree for carcinogenicity and mutagenicity. Our computational assessment showed that investigated chito-oligomers reflect promising pharmacological profiles and limited toxicological effects on humans, regardless of molecular weight, deacetylation degree, and acetylation pattern. According to our results, there is a possible inhibition of the organic anion transporting peptides OATP1B1 and/or OATP1B3, a weak potential of cardiotoxicity, a minor probability of affecting the androgen receptor, and phospholipidosis. Consequently, these results may be used to guide or to complement the existing in vitro and in vivo toxicity tests, to optimize biomaterials properties and to contribute to the selection of prototypes for nanocarriers.

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Section: Methodsmentioning

confidence: 99%

Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan

Roman

Som

et al. 2019

Front. Bioeng. Biotechnol.

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“…Prediction of ADMET profile is mainly based on models of the physicochemical properties of chemicals which influence much of their pharmacokinetics, but there are also prediction models of the endpoints in ADME that are based on both in vitro and in vivo assay results [23][24][25][26].…”

Section: K1 K2mentioning

confidence: 99%

Hydrosoluble and Liposoluble Vitamins: New Perspectives through ADMET Analysis

et al. 2021

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Background and Objectives: The present study demonstrates that apart from the well-known toxicity of liposoluble vitamins, some hydrosoluble vitamins may also exert toxicity; thus, routine supplementation with vitamins or ingestion of fortified foods should not be considered harmless. The study addresses the possible correlations between the physico-chemical properties and the side effects of vitamins when taken in high doses or for a too long a period. Materials and Methods: The FAFDrugs4.0 computational tool was used for computational assessment of the ADMET profile of several hydro- and liposoluble vitamins. Results: ADMET analysis revealed the following major data: vitamin B3 and B13 showed reduced structural complexity; thus, a relative toxicological potential may be exerted. Vitamins B1 and B7 were found to have good oral absorption and thus good bioavailability, while Vitamin B3 was found to have decreased oral absorption. In addition, all of the liposoluble vitamins reflected higher complexity, much greater than most of the potentially therapeutically-proven compounds. Conclusions: The present study emphasizes the importance between the physico-chemical properties of vitamins and their possible toxicological impact.

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“…Information acquired for every investigated sweetener has been synthetized and data are presented in Table I. In order to predict the pharmacokinetics and biological effects of these molecules we have used few accurate computational tools that were extensively used for assessing the biological or side effects of various chemicals: synthetic steroids [34], phthalates [10], oligomers of chitin, chitosan [35] and their derivatives [18], cosmetic ingredients and pesticides [2,16], low molecular weight oligomers of lactic acid [11] and of polydroxyalkanoates [36]. It highlights the applicability of these tools for predicting biological activity and toxicological endpoints for many classes of chemical compounds.…”

Section: Methodsmentioning

confidence: 99%

Computational Assessment of the Pharmacokinetics and Toxicity of the Intensive Sweeteners

Voiculescu¹

2021

FARMACIA

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The present study focuses on predicting the pharmacokinetics and toxicological endpoints of the widely used intensive sweeteners for preventing and management of diabetes: acesulfame K, advantame, aspartame, cyclamates, glycyrrhizin, neohesperidin dihydrochalcone, neotame, saccharin, steviol, sucralose, and tagatose. Predictions obtained using several computational tools were generally in good agreement each other and with few known data concerning the effects of these compounds on humans. The possible side effects produced by these sweeteners are: h-ERG blocking potential (glycyrrhizin, neohesperidin dihydrochalcone, advantame), eye and skin injuries (acesulfame K, cyclamates, saccharine), hepatotoxicity (saccharine), nephrotoxicity (steviol, glycyrrhizin), hypotension (advantame), mutagenicity and genotoxic carcinogenicity (acesulfame K, sucralose). RezumatPrezentul studiu se concentrează pe predicția profilurilor farmacocinetice și a efectelor toxicologice ale principalilor îndulcitori folosiți pentru prevenirea și gestionarea diabetului zaharat: acesulfam K, advantam, aspartam, ciclamați, glicirizină, neotam, neohesperidină, steviol, sucraloză, tagatoză și zaharină. Predicțiile obținute folosind mai multe instrumente computaționale au fost în general în concordanță și cu puținele date cunoscute cu privire la efectele acestor compuși asupra oamenilor. Posibilele efecte secundare produse de utilizarea îndulcitorilor investigați sunt: cardiotoxicitate prin inhibiția canalului de potasiu în mușchiul cardiac (glicirizina, neohesperidina, advantamul), leziuni oculare și cutanate (acesulfam K, ciclamați, zaharina), hepatotoxicitate (zaharina), nefrotoxicitate (steviolul, glicirizina), hipotensiune (advantamul), mutagenicitate și carcinogenitate genotoxică (acesulfam K, sucraloza).

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Prediction of ADME-Tox properties and toxicological endpoints of triazole fungicides used for cereals protection

Cited by 18 publications

References 37 publications

Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan

Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan

Hydrosoluble and Liposoluble Vitamins: New Perspectives through ADMET Analysis

Computational Assessment of the Pharmacokinetics and Toxicity of the Intensive Sweeteners

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