摘要
背景:惰剂框架被认为是药物化学和药物发现领域的特权结构之一,因为包含该框架的化合物已被证明具有与许多受体或蛋白质以高亲和力结合的显著能力。因此,惰性核是许多生物活性药物或药物中经常发现的部分也就不足为奇了。惰性衍生物因其抗结核特性也被探索或研究。肠道微生物群代谢物丙酸(IPA)对结核分枝杆菌(MTB)的生长抑制是最近的例子之一。值得注意的是,结核病(TB)是一种顽固性疾病,是世界范围内的主要死亡原因,由于两个主要原因,最近结核病病例数量惊人地上升。,在艾滋病毒感染者中增加了几倍,一些菌株的耐药性增加了。因此,迫切需要识别针对结核病的新药物或潜在药物。 方法:虽然许多惰性衍生物的抗结核活性的特定药理靶点或作用机制(MOA)已被报道,但MOA对许多惰性衍生物具有结核活性,但它们被发现对结核有活性。在当前的综述文章中,我们关注两种类型的惰性衍生物,显示活动对MTB已知支持进一步分离基于这个药理目标报道或指出而其他惰性根据显示的抗结核特性的类型分类。在2020年8月之前,在Pubmed、谷歌学者、医学和其他各种数据库上检索过去20年的文献以及最新的知识和信息。 结果:各种功能化惰剂衍生物如生物碱、简单惰碱、融合惰剂、酰胺/肽衍生物、异素衍生物等均具有抗结核活性。本文简要介绍了硅研究中的抗结核活性(如果有报道)和具有代表性的惰性衍生物的化学合成(在大多数情况下)。这篇综述引用的论文允许对过去20年探索的基于结肠的抗结核药物的状态进行深入分析。 结论:本综述旨在激发人们重新发现和开发新的惰性药物或潜在药物的兴趣和努力。现代方法的出现,特别是那些基于过渡金属催化反应的方法的出现,为惰剂合成领域开辟了巨大的机会。所期望的目标将是利用这些现代方法来确定有效和有前途的药物来对抗分枝结核杆菌。
关键词: 惰性,结核病,合成,在硅中,在体外,在体内。
Current Medicinal Chemistry
Title:Indole Derivatives as Anti-Tubercular Agents: An Overview on their Synthesis and Biological Activities
Volume: 28 Issue: 22
关键词: 惰性,结核病,合成,在硅中,在体外,在体内。
摘要:
Background: The indole framework is considered as one of the privileged structures in the area of medicinal chemistry and drug discovery because compounds containing this framework have shown to possess a remarkable ability to bind with many receptors or proteins with high affinity. It is therefore not surprising that the indole nucleus is a frequently found moiety in many bioactive agents or drugs. Indole derivatives have also been explored or studied for their anti-tubercular properties for a long time. The growth inhibition of Mycobacterium tuberculosis (MTB) in vitro and in vivo by the gut microbiota metabolite indole propionic acid (IPA) is one of the recent examples. Notably, tuberculosis (TB), an intractable disease and a major cause of death worldwide, has caused an alarming rise in the number of TB cases recently because of two main reasons, i.e., a several-fold rise among HIV-infected patients and increased drug resistance by some bacterial strains. Thus, the identification of new agents or potential drugs against TB is urgently needed.
Methods: While the specific pharmacological target or mechanism of action (MOA) for antitubercular activities has been reported for many indole derivatives, the MOA is not well defined or known for a number of indole derivatives though they were found to be active against MTB. In the current review article, we have focused on both types of indole derivatives that have shown activities against MTB. The indoles with known MOA are further segregated based on this pharmacological target reported or indicated whereas other indoles are classified based on the type of anti-TB properties shown by them. The literature for the last 20 years as well as related to up to date knowledge and information was searched on Pubmed, Google Scholar, MEDLINE, and various other databases until August 2020.
Results: A diverse range of functionalized indole derivatives, such as indole-based alkaloids, simple indoles, fused indoles, amide/peptide derivatives of indole, isatin derivatives, etc., have been reported to possess anti-tubercular activities. The anti-tubercular activities, in silico studies (if reported) and the chemical syntheses (in most of the cases) of representative indole derivatives are presented briefly in the current article. The papers referenced by this review allow a deep analysis of the status of the indole-based anti-tubercular agents explored over the past two decades.
Conclusion: This review aims at stimulating renewed interest and effort in the discovery and development of new indole-based agents or potential drugs for the treatment of TB. The emergence of modern methods, especially those based on transition metal-catalyzed reactions, has opened up tremendous opportunities in the area of indole synthesis. The desired goal would be to have utilized these modern methodologies for the identification of potent and promising agents to fight against MTB.
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Indole Derivatives as Anti-Tubercular Agents: An Overview on their Synthesis and Biological Activities, Current Medicinal Chemistry 2021; 28 (22) . https://dx.doi.org/10.2174/0929867327666200918144709
DOI https://dx.doi.org/10.2174/0929867327666200918144709 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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