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天然萘醌及其衍生物作为抗锥虫寄生虫的潜在药物分子。

Natural naphthoquinones and their derivatives as potential drug molecules against trypanosome parasites.

作者信息

Rani Ruma, Sethi Khushboo, Kumar Sanjay, Varma Rajender S, Kumar Rajender

机构信息

ICAR-National Research Centre on Equines, Hisar, India.

Regional Center of Advanced Technologies and Materials, Palacky University, Olomouc, Czech Republic.

出版信息

Chem Biol Drug Des. 2022 Dec;100(6):786-817. doi: 10.1111/cbdd.14122. Epub 2022 Jul 27.

DOI:10.1111/cbdd.14122
PMID:35852920
Abstract

Over the past decades, a number of 1,4-naphthoquinones have been isolated from natural resources and several of naphthoquinone derivatives with diverse structural motif have been synthesized; they possess a multitude of biochemical properties and modulate numerous pharmacological roles that offer new targets for addressing the challenges pertaining to novel drug developments. Among natural naphthoquinones, lapachol, α-lapachone, β-lapachone, lawsone, juglone, and plumbagin have been evaluated for its potential as antitrypanosomal activities. The chemotherapeutic drugs available for combating human trypanosomiasis, that is, American trypanosomiasis and African trypanosomiasis caused by Trypanosoma cruzi and Trypanosoma brucei, respectively, and animal tripanosomosis caused by Trypanosoma evansi have a problem of drug resistance and several toxic effect. Therefore, search of alternative effective drug molecules, without toxic effects, have enthused the researchers for searching new drug entity with potential clinical efficacy. In the search for new antitrypanosomal compound, this review focuses on different natural quinones and their synthetic derivatives associated with antitrypanosomal studies. In this context, this review will be useful for the development of new antitrypanosomal drugs mainly based on different structural modification of natural and synthetic naphthoquinones.

摘要

在过去几十年中,已从自然资源中分离出多种1,4-萘醌,并合成了几种具有不同结构 motif 的萘醌衍生物;它们具有多种生化特性,并发挥多种药理作用,为应对新型药物开发面临的挑战提供了新靶点。在天然萘醌中,拉帕醇、α-拉帕酮、β-拉帕酮、紫铆因、胡桃醌和白花丹素已被评估其作为抗锥虫活性的潜力。用于对抗人类锥虫病(即分别由克氏锥虫和布氏锥虫引起的美洲锥虫病和非洲锥虫病)以及由伊氏锥虫引起的动物锥虫病的化疗药物存在耐药性问题和多种毒性作用。因此,寻找无毒副作用的替代有效药物分子激发了研究人员寻找具有潜在临床疗效的新药物实体的热情。在寻找新的抗锥虫化合物的过程中,本综述重点关注与抗锥虫研究相关的不同天然醌及其合成衍生物。在此背景下,本综述对于主要基于天然和合成萘醌的不同结构修饰开发新的抗锥虫药物将是有用的。

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