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新型恶二唑衍生物在急性和亚急性毒性研究中的安全性评估。

Safety assessment of novel oxadiazole derivatives in acute and sub-acute toxicity studies.

作者信息

Zainab Syeda Rida, Khan Jehan Zeb, Nadeem Humaira, Tipu Muhammad Khalid, Irshad Nadeem

机构信息

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan.

Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):3631-3653. doi: 10.1007/s00210-024-03474-0. Epub 2024 Oct 1.

Abstract

1,3,4-Oxadiazole is a fascinating heterocyclic compound with a unique five-membered ring structure containing nitrogen and oxygen atoms. It has garnered significant attention for its interactions and activities within biological systems. This versatility has led to the production of several ligands using this compound as a pharmacophore. This study evaluates the acute toxicity of three oxadiazole derivatives (1,3,4-Bromo, Chloro, and Iodo) followed by a 28 days sub-acute study involving four different doses of each derivative. The study followed the guideline, the Organization for Economic Cooperation and Development (OECD) outlined, specifically OECD Guidelines 425 for the acute toxicity study and OECD Guidelines 407 for the sub-acute study. In the acute toxicity study, a high dose of 2000 mg/kg was administered to male and female rats to establish lethal dose 50 (LD50) values, and the rats were closely monitored for 14 days. The subsequent sub-acute study involved the administration of four different doses (1.25, 2.5, 5, and 10 mg/kg) of each derivative to male and female rats for 28 days. Throughout both studies, careful monitoring for signs of toxicity and comprehensive hematological, biochemical, and histological analysis were carried out thoroughly. The results of the acute toxicity study indicated that all three derivatives had LD50 values exceeding 2000 mg/kg, and the rats did not display significant signs of toxicity. Similarly, no organ or systemic toxicity was observed in the repeated dose sub-acute study for any of the three derivatives. In conclusion, based on the findings of these studies, it was determined that the derivatives are safe for further investigation of their pharmacological activity.

摘要

1,3,4-恶二唑是一种迷人的杂环化合物,具有独特的含氮和氧原子的五元环结构。它因其在生物系统中的相互作用和活性而备受关注。这种多功能性导致了几种以该化合物作为药效基团的配体的产生。本研究评估了三种恶二唑衍生物(1,3,4-溴、氯和碘)的急性毒性,随后进行了一项为期28天的亚急性研究,涉及每种衍生物的四种不同剂量。该研究遵循了经济合作与发展组织(OECD)概述的指南,具体而言,急性毒性研究遵循OECD指南425,亚急性研究遵循OECD指南407。在急性毒性研究中,对雄性和雌性大鼠给予2000 mg/kg的高剂量以确定半数致死剂量(LD50)值,并对大鼠进行了14天的密切监测。随后的亚急性研究涉及对雄性和雌性大鼠给予每种衍生物的四种不同剂量(1.25、2.5、5和10 mg/kg),持续28天。在两项研究中,都对毒性迹象进行了仔细监测,并全面进行了血液学、生化和组织学分析。急性毒性研究结果表明,所有三种衍生物的LD50值均超过2000 mg/kg,大鼠未表现出明显的毒性迹象。同样,在重复剂量亚急性研究中,三种衍生物中的任何一种都未观察到器官或全身毒性。总之,基于这些研究的结果,确定这些衍生物对于进一步研究其药理活性是安全的。

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