ADME-Tox profiling of some water soluble chitosan derivatives

Isvoran, Adriana; Ciorsac, Alecu; Ostafe, Vasile

doi:10.5599/admet.5.3.423

Cited by 18 publications

(11 citation statements)

References 26 publications

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“…To the best of our knowledge, this approach has never been conducted before. Similar studies have been performed for xenobiotics such as food supplements, steroids, food additives, and pesticides, revealing valuable results [30][31][32].…”

Section: K1 K2mentioning

confidence: 59%

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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Section: K1 K2mentioning

confidence: 59%

Hydrosoluble and Liposoluble Vitamins: New Perspectives through ADMET Analysis

et al. 2021

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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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“…It also conducted to the development of various computational tools that can be used for hazard assessment. They are recognized by the Organization of Economic and Cooperation Development (OECD) [15] and European Food Safety Association [16] and are constantly used nowadays in assessing the toxicological effects of various chemicals on humans [17][18][19][20][21]. Besides the large applicability of these tools for human hazard assessment, there are some limitations mostly related to the predictability of training models and to the fact that they do not take into account the dose.…”

Section: Introductionmentioning

confidence: 99%

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

2019

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<p class="ADMETabstracttext">Within this study we have considered 9 triazole fungicides that are approved to be used in European Union for protecting cereals: cyproconazole, epoxiconazole, flutriafol, metconazole, paclobutrazole, tebuconazole, tetraconazole, triadimenol and triticonazole. We have summarized the few available data that support their effects on humans and used various computational tools to obtain a widely view concerning their possible harmful effects on humans. The results of our predictive study reflect that all triazole fungicides considered in this study reveal good oral bioavailability, are envisaged as being able to penetrate the blood brain barrier and to interact with P-glycoprotein and with hepatic cytochromes. The predictions concerning the toxicological endpoints for the investigated triazole fungicides reveal that they. reflect potential of skin sensitization, of blockage of the hERG K+ channels and of endocrine disruption, that they have not mutagenic potential and their carcinogenic potential is not clear. Epoxiconazole and triadimenol are predicted to have the highest potentials of producing numerous harmful effects on humans and their use should be avoided or limited. </p>

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ADME-Tox profiling of some water soluble chitosan derivatives

Abstract: Within this study we use a few computational tools for predicting absorption, distribution, metabolism, excretion and toxicity (ADME-Tox)

Cited by 18 publications

References 26 publications

Hydrosoluble and Liposoluble Vitamins: New Perspectives through ADMET Analysis

Hydrosoluble and Liposoluble Vitamins: New Perspectives through ADMET Analysis

Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan

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

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