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乙酰氨基阿维菌素——一种古老的抗寄生虫药物:药理学与治疗学进展

Diminazene aceturate--An antiparasitic drug of antiquity: Advances in pharmacology & therapeutics.

作者信息

da Silva Oliveira George Laylson, de Freitas Rivelilson Mendes

机构信息

Department of Pharmacy, Federal University of Piauí, Teresina, Piauí 64049-550, Brazil.

出版信息

Pharmacol Res. 2015 Dec;102:138-57. doi: 10.1016/j.phrs.2015.10.005. Epub 2015 Oct 22.

Abstract

Diminazene aceturate (C14H15N7.2C4H7NO3) is an aromatic diamidine that was developed more than six decades ago and has been marketed until today for the control of trypanosomiasis. In recent years, however, this trypanocidal compound has been extensively studied with respect to its therapeutic potential and has consequently attracted much interest for the development of further research. The objective of this study was to conduct a systematic review on diminazene aceturate regarding its pharmacological properties. In this way, databases were searched for articles (ScienceDirect, Scopus, PubMed, Web of Science and SciFinder) and patents (INPI, USPTO, WIPO, DPMA, SIPO, DERWENT, CIPO and EPO). For the development of this review, 115 articles and 22 patents were selected and analyzed. It was thus possible to highlight several researches that have investigated alternatives in order to improve success in the treatment of animal trypanosomiasis, by using new drugs in associations with diminazene aceturate, as well as looking for new pharmacological applications for this compound, such as leishmanicidal, amebicidal, anti-pneumocystis, anti-rheumatoid arthritis, antihypertensive agent, and mainly as an activator of angiotensin-converting enzyme 2. Another pharmacological property still little studied is the inhibition of acid-sensitive ion channels (ASIC1a, ASIC1b, ASIC2a and ASIC3), which are related to the development of various diseases. Collectively, these studies conducted by several research groups extend the use of diminazene aceturate beyond the antitrypanosomal activity and suggest promising new applications.

摘要

乙酰甘氨酸二脒那嗪(C14H15N7.2C4H7NO3)是一种芳香族二脒,六十多年前就已研发出来,至今仍在市场上用于治疗锥虫病。然而,近年来,这种杀锥虫化合物在其治疗潜力方面得到了广泛研究,因此吸引了更多开展进一步研究的兴趣。本研究的目的是对乙酰甘氨酸二脒那嗪的药理特性进行系统综述。通过这种方式,在数据库(科学Direct、Scopus、PubMed、科学网和SciFinder)和专利库(巴西国家工业产权局、美国专利商标局、世界知识产权组织、德国专利商标局、中国国家知识产权局、德温特、加拿大知识产权局和欧洲专利局)中搜索文章和专利。为开展本综述,挑选并分析了115篇文章和22项专利。因此,可以突出几项研究,这些研究调查了多种替代方法,以便通过将新药与乙酰甘氨酸二脒那嗪联合使用来提高动物锥虫病治疗的成功率,同时也在寻找该化合物的新药理应用,如抗利什曼原虫、抗阿米巴、抗肺孢子虫病、抗类风湿性关节炎、抗高血压药物,主要是作为血管紧张素转换酶2的激活剂。另一种研究较少的药理特性是对酸敏感离子通道(ASIC1a、ASIC1b、ASIC2a和ASIC3)的抑制作用,这些通道与多种疾病的发生发展有关。多个研究小组开展的这些研究共同扩展了乙酰甘氨酸二脒那嗪在抗锥虫活性之外的用途,并提示了有前景的新应用。

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