Naunyn Schmiedebergs Arch Pharmacol
January 2025
Establishing the safety of impurities in drug substances or products is crucial. The assessment of genotoxicity for these impurities and determining the acceptable limits pose considerable challenges, as recognized in recent guidelines. While the genotoxicity profile of vildagliptin-an oral hypoglycemic drug-is well established, there is limited knowledge about the genotoxic potential of its impurities.
View Article and Find Full Text PDFFullerene derivatives (FDs) are widely used in nanomaterials production, the pharmaceutical industry and biomedicine. In the present study, we focused on the potential toxic effects of FDs on the aquatic environment. First, we analyzed the binding affinity of 169 FDs to 10 human proteins (1D6U, 1E3K, 1GOS, 1GS4, 1H82, 1OG5, 1UOM, 2F9Q, 2J0D, 3ERT) obtained from the Protein Data Bank (PDB) and showing high similarity to proteins from aquatic species.
View Article and Find Full Text PDFFullerene derivatives (FDs) belong to a relatively new family of nano-sized organic compounds. They are widely applied in materials science, pharmaceutical industry, and (bio) medicine. This research focused on the study of FDs in terms of their potential inhibitory effect on therapeutic targets associated with diabetic disease, as well as analysis of protein-ligand binding in order to identify the key binding characteristics of FDs.
View Article and Find Full Text PDFObjectives: 4-(2-fluorophenoxy) quinoline derivatives constitute one of the chemical classes of hepatocyte growth factor receptor (c-MET) inhibitors, a promising treatment against various human tumors. There are three aims of the present study: (1) To develop a robust and validated quantitative structure-activity relationship model to predict the c-Met kinase inhibition; (2) to examine the toxicity profiles of these compounds; (3) to design new quinoline derivatives and apply the developed model on these compounds to observe its pertinence.
Materials And Methods: A multiple linear regression method was used to develop the model with calculated descriptors.
This study aimed to obtain necessary toxicological data using experimental and computational methods for the calculation of a common permitted daily exposure (PDE) which can be relevant for nicotinic acid and its esters and nicotinamide according to European Medicines Agency Guideline on setting health-based exposure limits. PDE calculation is mainly based on critical toxicological endpoints. During this procedure, critical toxicological endpoints data of an active pharmaceutical ingredient (API) may not be able to find satisfactorily.
View Article and Find Full Text PDFFood Chem Toxicol
November 2020
Herbal products as supplements and therapeutic intervention have been used for centuries. However, their toxicities are not completely evaluated and the mechanisms are not clearly understood. Dried rhizome of the plant kava (Piper methysticum) is used for its anxiolytic, and sedative effects.
View Article and Find Full Text PDFdesignates two poets coincidently writing a same verse in the Ottoman Divan literature. This study aims to analyze the structural similarity of molecules independently designed for inflammation and depression to determine if coincidentally we are building similar molecules for comorbid diseases. For this purpose, a molecule library was first constituted with structures that were developed as anti-inflammatory (AI) and antidepressant (AD) agents these last decades.
View Article and Find Full Text PDFPredictive toxicology plays an integral role in determining the toxicological profiles of chemicals for safety assessment. Vitamin D is an essential vitamin for the regulation of calcium absorption and homeostasis, as well as the treatment and prevention of several diseases such as rickets and osteomalacia. According to European Medicines Agency (EMA) Guideline on setting health-based exposure limits for use in risk identification in the manufacturing of different medicinal products in shared facilities, permitted daily exposure (PDE) calculation for active pharmaceutical ingredients (APIs) should be done by the medicinal product producers.
View Article and Find Full Text PDFBackground: The discovery of novel potent molecules for both cancer prevention and treatment has been continuing over the past decade. In recent years, identification of new, potent, and safe anticancer agents through drug repurposing has been regarded as an expeditious alternative to traditional drug development. The cyclooxygenase-2 is known to be over-expressed in several types of human cancer.
View Article and Find Full Text PDFIn this publication, QSAR models were developed to predict analgesic and anti-inflammatory activities of some 2-benzoxazolinone derivatives using multiple linear regression method. The models were validated internally and externally according to the OECD principles. With the help of these models, pronounced molecular properties of these compounds related to activities were also explored.
View Article and Find Full Text PDFAcyl glucuronidation is an important Phase II biotransformation, which is an efficient detoxification mechanism for the metabolism of carboxylic acid group-containing drugs. However, the reactivity of acyl glucuronide (AG) metabolites associated with short half-lives may be an indication of idiosyncratic drug toxicity. The degradation half-lives of AGs elucidate several important reactions such as hydrolysis, acyl migration and covalent binding to proteins.
View Article and Find Full Text PDFFood Chem Toxicol
August 2018
Epinephrine and norepinephrine have been used in the management of anaphylactic reactions and cardiac resuscitation, along with treatment of asthma and glaucoma extensively, but their toxicological profiles are not yet completed. Based on this circumstance, various toxicological endpoints of epinephrine and norepinephrine were explored. Since there is a paucity of some endpoints' data, readacross was applied to fill the data gaps using analog approach.
View Article and Find Full Text PDFEnvironmental risk assessment procedures require acute and chronic toxicity values of hazardous chemicals. In this respect, the 96-h toxicity bioassays of nitro-, methyl-, methoxy-, chloro-, and nitrile- substituted phenols and anilines to Chlorella vulgaris were performed. Median inhibitory and low-toxic-effect concentrations were reported.
View Article and Find Full Text PDFThis study provides for the first time the 96-h toxicity of 16 nitro- and methyl- substituted phenols to Chlorella vulgaris. Enabling the circulation of new ecotoxicity data has expanded the previously reported toxicity data set of 30 phenols to C. vulgaris by our laboratory.
View Article and Find Full Text PDFThis study presents quantitative structure-toxicity relationship (QSTR) models on the toxicity of 91 organic compounds to Chlorella vulgaris using multiple linear regression (MLR) and Kriging techniques. The molecular descriptors were calculated using SPARTAN and DRAGON programs, and descriptor selection was made by "all subset" method available in the QSARINS software. MLR and Kriging models developed with the same descriptors were compared.
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