Toxicological evaluation of imidazo-based heterocyclic derivatives: In-vitro and in-vivo acute toxicity studies

Q1 Environmental Science
Sunil Kumar , Ajay Singhal , Pankaj Kumar , Manish Jain , Manpreet Kaur , Ishika Gupta , Deepak B. Salunke , Sandip V. Pawar
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引用次数: 0

Abstract

Imidazo based heterocyclic derivatives are considered as privileged scaffolds due to their presence in various pharmacologically active compounds and in marketed formulations. The present study reports toxicological evaluation of three imidazo based heterocyclic derivatives which are currently being investigated for their potential anticancer activity. Compounds IG-01–007, IG-01–008, and IG-01–009 were assessed for cytotoxicity, hemolysis, and DNA fragmentation activity. Acute oral toxicity studies were performed at doses of 300 mg/kg and 1000 mg/kg according to OECD guidelines, in both male and female Wistar rats. All test compounds at a concentration of 50 µM resulted in DNA fragmentation suggesting notable impact on DNA integrity. The in-vivo acute toxicity study indicated significant toxicity at doses of ≥ 1000 mg/kg, particularly for compounds IG-01–008 and IG-01–009, which caused hepatic damage and cholestasis in liver tissues. These results collectively suggest that imidazo based heterocyclic derivatives used in the present study exhibit cytotoxic potential.
咪唑基杂环衍生物的毒理学评价:体外和体内急性毒性研究。
咪唑基杂环衍生物被认为是优越的支架,因为它们存在于各种药理学活性化合物和上市制剂中。本研究报告了三种咪唑基杂环衍生物的毒理学评价,这些衍生物目前正在研究其潜在的抗癌活性。对化合物IG-01-007、IG-01-008和IG-01-009进行细胞毒性、溶血和DNA断裂活性评估。根据经合组织指南,对雄性和雌性Wistar大鼠进行了300 mg/kg和1000 mg/kg剂量的急性口服毒性研究。所有测试化合物在浓度为50 µM时都导致DNA断裂,表明对DNA完整性有显著影响。体内急性毒性研究表明,剂量≥ 1000 mg/kg时具有显著毒性,特别是化合物IG-01-008和IG-01-009,可引起肝组织损伤和胆汁淤积。这些结果共同表明,在本研究中使用的咪唑基杂环衍生物具有细胞毒性潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Toxicology Reports
Toxicology Reports Environmental Science-Health, Toxicology and Mutagenesis
CiteScore
7.60
自引率
0.00%
发文量
228
审稿时长
11 weeks
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