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2-羟基-3-苯胺基-1,4-萘醌衍生物的细胞毒性、溶血作用及急性毒性

Cytotoxicity, hemolysis and acute toxicity of 2-hydroxy-3-anilino-1,4-naphthoquinone derivatives.

作者信息

de Sena Pereira Valeska Santana, Silva de Oliveira Cláudio Bruno, Fumagalli Fernando, da Silva Emery Flávio, da Silva Naisandra Bezerra, de Andrade-Neto Valter F

机构信息

Laboratory of Malaria and Toxoplasmosis Biology, Department of Microbiology and Parasitology, Federal University of Rio Grande do Norte, Natal, RN, Brazil.

Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

出版信息

Toxicol Rep. 2016 Sep 16;3:756-762. doi: 10.1016/j.toxrep.2016.09.007. eCollection 2016.

Abstract

The 1,4-naphthoquinones, important members of the family of quinones are used as both crude extracts and as compound manipulated by the pharmaceutical industry. They have gained great emphasis by presenting different pharmacological properties as antibacterial, antiviral, antiprotozoal and anthelmintic, and has antitumor activity. Our aim was to evaluate the cytotoxicity, hemolytic activity and acute toxicity of three derivatives of 2-hydroxy-1,4-naphthoquinones. The cell viability against RAW Cell Line displayed IC ranging of 483.5-2044.8 μM, whereas in primary culture tests using murine macrophages, IC were 315.8-1408.0 μM for naphthoquinones derivatives and respectively, besides no hemolysis was observed at the dose tested. The acute toxicity assays exhibited a significant safety margin indicated by a lack of systemic and behavioral toxicity up to 300 mg/kg, and at a dose of 1000 mg/kg the derivatives not triggering signs of toxicity although the compound have promoted hepatic steatosis and hyperemia in kidney tissue. Thereby, these modifications decrease the toxicity of the tested derivatives naphthoquinones, providing a high potential for the development of news drugs.

摘要

1,4-萘醌是醌类家族的重要成员,既以粗提物形式使用,也作为制药行业加工的化合物使用。它们因具有抗菌、抗病毒、抗原虫和驱虫等不同药理特性以及抗肿瘤活性而备受关注。我们的目的是评估三种2-羟基-1,4-萘醌衍生物的细胞毒性、溶血活性和急性毒性。针对RAW细胞系的细胞活力显示IC范围为483.5 - 2044.8 μM,而在使用小鼠巨噬细胞的原代培养试验中,萘醌衍生物的IC分别为315.8 - 1408.0 μM,并且在所测试剂量下未观察到溶血现象。急性毒性试验显示出显著的安全边际,高达300 mg/kg时未出现全身和行为毒性迹象,在1000 mg/kg剂量下,尽管该化合物导致肝脂肪变性和肾组织充血,但衍生物未引发毒性迹象。因此,这些修饰降低了所测试的萘醌衍生物的毒性,为新药开发提供了很高的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b72d/5617738/e1d5d96b2eb1/gr1.jpg

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