Kumar Sunil, Singhal Ajay, Kumar Pankaj, Jain Manish, Kaur Manpreet, Gupta Ishika, Salunke Deepak B, Pawar Sandip V
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
Department of Chemistry and Centre of Advanced Studies, Panjab University, Chandigarh 160014, India.
Toxicol Rep. 2024 Dec 16;14:101872. doi: 10.1016/j.toxrep.2024.101872. eCollection 2025 Jun.
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 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.
基于咪唑的杂环衍生物因其存在于各种具有药理活性的化合物和市售制剂中而被视为特权骨架。本研究报告了三种基于咪唑的杂环衍生物的毒理学评估，目前正在对其潜在的抗癌活性进行研究。对化合物IG-01-007、IG-01-008和IG-01-009进行了细胞毒性、溶血和DNA片段化活性评估。根据经合组织指南，在雄性和雌性Wistar大鼠中以300mg/kg和1000mg/kg的剂量进行急性口服毒性研究。所有浓度为50µM的受试化合物均导致DNA片段化，表明对DNA完整性有显著影响。急性毒性研究表明，剂量≥1000mg/kg时具有显著毒性，特别是化合物IG-01-008和IG-01-009，它们在肝脏组织中引起肝损伤和胆汁淤积。这些结果共同表明，本研究中使用的基于咪唑的杂环衍生物具有细胞毒性潜力。
