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作为潜在的抗寄生虫药物,喹喔啉和喹喔啉 1,4-二 N-氧化物衍生物的研究现状。

Current status of quinoxaline and quinoxaline 1,4-di-N-oxides derivatives as potential antiparasitic agents.

机构信息

Sección de Estudios de Posgrado e Investigación, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, Ciudad de México, México.

Instituto Colombiano de Medicina Tropical, Universidad CES, Antioquia, Colombia.

出版信息

Chem Biol Drug Des. 2021 Oct;98(4):683-699. doi: 10.1111/cbdd.13921. Epub 2021 Jul 21.

Abstract

Parasitic diseases are a public health problem, especially in developing countries where millions of people are affected every year. Current treatments have several drawbacks: emerging resistance to the existing drugs, lack of efficacy, and toxic side effects. Therefore, new antiparasitic drugs are urgently needed to treat and control diseases that affect human health, such as malaria, Chagas disease, leishmaniasis, amebiasis, giardiasis schistosomiasis, and filariasis, among others. Quinoxaline is a compound containing a benzene ring and a pyrazine ring. The oxidation of both pyrazine ring nitrogens allows the obtention of quinoxaline 1,4-di-N-oxides (QdNOs) derivatives. By modifying the chemical structure of these compounds, it is possible to obtain a wide variety of biological properties. This review investigated the activity of quinoxaline derivatives and QdNOs against different protozoan parasites and helminths. We also cover the structure-activity relationship (SAR) and summarize the main findings related to their mechanisms of action from published works in recent years. However, further studies are needed to determine specific molecular targets. This review aims to highlight the new development of antiparasitic drugs with better pharmacological profiles than current treatments.

摘要

寄生虫病是一个公共卫生问题,特别是在发展中国家,每年都有数百万人受到影响。目前的治疗方法存在几个缺点:现有药物的耐药性不断出现、疗效不佳和有毒的副作用。因此,迫切需要新的抗寄生虫药物来治疗和控制影响人类健康的疾病,如疟疾、恰加斯病、利什曼病、阿米巴病、贾第虫病、血吸虫病和丝虫病等。喹喔啉是一种含有苯环和吡嗪环的化合物。两个吡嗪环氮的氧化可以得到喹喔啉 1,4-二-N-氧化物(QdNOs)衍生物。通过修饰这些化合物的化学结构,可以获得各种各样的生物特性。本综述研究了喹喔啉衍生物和 QdNOs 对不同原生动物寄生虫和蠕虫的活性。我们还涵盖了构效关系(SAR),并总结了近年来发表的相关工作中关于其作用机制的主要发现。然而,仍需要进一步的研究来确定特定的分子靶点。本综述旨在强调具有比现有治疗方法更好的药理学特性的新型抗寄生虫药物的新发展。

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