几个世纪以来,天然产物(NPs)已作为强大的治疗各种人类疾病。如今,它们仍然是治疗许多疾病的宝贵资源,包括细菌感染。在世界卫生组织(WHO)宣布结核病(TB)为全球卫生紧急情况近三十年后,结核分枝杆菌(Mtb)继续夺去数百万人的生命,仍然是全球主要的死亡原因之一。在过去的几年里,已经做出了一些努力来缩短和改善治疗结果,并克服不断增加的阻力现象。大自然总是提供几乎无限的生物活性分子来源,这激发了新药的开发。NPs的特点是特殊的化学和结构多样性,千年进化对各种刺激反应的结果。由于其有利的结构特征和酶的起源,它们天然易于结合蛋白质并表现出生物活性。此外,它们在全球范围内的分布和无障碍环境有助于促进对其活动的调查。总的来说,这些特性使NP成为设计新疗法的优秀模型。这篇综述提供了最有前途的NP的关键和全面的概述,从植物中分离出来,真菌,海洋物种,和细菌,具有对传统和新兴分枝杆菌酶靶标的抑制特性。这里讨论了86种化合物的选择,特别强调它们的生物活性,结构-活动关系,和作用机制。我们的研究证实了NPs的抗分枝杆菌潜力,证实它们在未来药物发现和开发工作中的相关性。
For centuries, natural products (NPs) have served as powerful therapeutics against a variety of human ailments. Nowadays, they still represent invaluable resources for the treatment of many diseases, including bacterial infections. After nearly three decades since the World Health Organization\'s (WHO) declaration of tuberculosis (TB) as a global health emergency, Mycobacterium tuberculosis (Mtb) continues to claim millions of lives, remaining among the leading causes of death worldwide. In the last years, several efforts have been devoted to shortening and improving treatment outcomes, and to overcoming the increasing resistance phenomenon. Nature has always provided a virtually unlimited source of bioactive molecules, which have inspired the development of new drugs. NPs are characterized by an exceptional chemical and structural diversity, the result of millennia of evolutionary responses to various stimuli. Thanks to their favorable structural features and their enzymatic origin, they are naturally prone to bind proteins and exhibit bioactivities. Furthermore, their worldwide distribution and ease of accessibility has contributed to promote investigations on their activity. Overall, these characteristics make NPs excellent models for the design of novel therapeutics. This review offers a critical and comprehensive overview of the most promising NPs, isolated from plants, fungi, marine species, and bacteria, endowed with inhibitory properties against traditional and emerging mycobacterial enzymatic targets. A selection of 86 compounds is here discussed, with a special emphasis on their biological activity, structure-activity relationships, and mechanism of action. Our study corroborates the antimycobacterial potential of NPs, substantiating their relevance in future drug discovery and development efforts.