{"title":"对阿齐沙坦光产物诱变性的硅学和体外评估。","authors":"Takahiro Yoshikawa , Naoto Hayashi , Masayuki Yokota","doi":"10.1016/j.mrgentox.2024.503841","DOIUrl":null,"url":null,"abstract":"<div><div>Photodegradation of azilsartan yields a phenanthridine derivative (APP). We suspected that APP could be a DNA-reactive substance, since many phenanthridine derivatives are mutagenic. In silico quantitative structure-activity relationship analysis indicated potential mutagenicity of APP, due to DNA reactivity at the 6-aminophenanthridine moiety. However, APP was not mutagenic in the Ames test. Density functional theory (DFT) calculations showed that APP cannot intercalate into DNA, due to its nonplanar structure, resulting from steric hindrance of its phenanthridine and benzimidazole moieties.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"901 ","pages":"Article 503841"},"PeriodicalIF":2.5000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"In silico and in vitro assessments of the mutagenicity of the azilsartan photoproduct\",\"authors\":\"Takahiro Yoshikawa , Naoto Hayashi , Masayuki Yokota\",\"doi\":\"10.1016/j.mrgentox.2024.503841\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Photodegradation of azilsartan yields a phenanthridine derivative (APP). We suspected that APP could be a DNA-reactive substance, since many phenanthridine derivatives are mutagenic. In silico quantitative structure-activity relationship analysis indicated potential mutagenicity of APP, due to DNA reactivity at the 6-aminophenanthridine moiety. However, APP was not mutagenic in the Ames test. Density functional theory (DFT) calculations showed that APP cannot intercalate into DNA, due to its nonplanar structure, resulting from steric hindrance of its phenanthridine and benzimidazole moieties.</div></div>\",\"PeriodicalId\":18799,\"journal\":{\"name\":\"Mutation research. Genetic toxicology and environmental mutagenesis\",\"volume\":\"901 \",\"pages\":\"Article 503841\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mutation research. Genetic toxicology and environmental mutagenesis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1383571824001177\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/24 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mutation research. Genetic toxicology and environmental mutagenesis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1383571824001177","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/24 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
In silico and in vitro assessments of the mutagenicity of the azilsartan photoproduct
Photodegradation of azilsartan yields a phenanthridine derivative (APP). We suspected that APP could be a DNA-reactive substance, since many phenanthridine derivatives are mutagenic. In silico quantitative structure-activity relationship analysis indicated potential mutagenicity of APP, due to DNA reactivity at the 6-aminophenanthridine moiety. However, APP was not mutagenic in the Ames test. Density functional theory (DFT) calculations showed that APP cannot intercalate into DNA, due to its nonplanar structure, resulting from steric hindrance of its phenanthridine and benzimidazole moieties.
期刊介绍：
Mutation Research - Genetic Toxicology and Environmental Mutagenesis (MRGTEM) publishes papers advancing knowledge in the field of genetic toxicology. Papers are welcomed in the following areas:
New developments in genotoxicity testing of chemical agents (e.g. improvements in methodology of assay systems and interpretation of results).
Alternatives to and refinement of the use of animals in genotoxicity testing.
Nano-genotoxicology, the study of genotoxicity hazards and risks related to novel man-made nanomaterials.
Studies of epigenetic changes in relation to genotoxic effects.
The use of structure-activity relationships in predicting genotoxic effects.
The isolation and chemical characterization of novel environmental mutagens.
The measurement of genotoxic effects in human populations, when accompanied by quantitative measurements of environmental or occupational exposures.
The application of novel technologies for assessing the hazard and risks associated with genotoxic substances (e.g. OMICS or other high-throughput approaches to genotoxicity testing).
MRGTEM is now accepting submissions for a new section of the journal: Current Topics in Genotoxicity Testing, that will be dedicated to the discussion of current issues relating to design, interpretation and strategic use of genotoxicity tests. This section is envisaged to include discussions relating to the development of new international testing guidelines, but also to wider topics in the field. The evaluation of contrasting or opposing viewpoints is welcomed as long as the presentation is in accordance with the journal''s aims, scope, and policies.
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