Laboratório de Síntese de Moléculas Medicinais (LaSMMed), Departamento de Química, Centro de Ciências Exatas, Universidade Estadual de Londrina, Londrina, Brazil.
Curr Med Chem. 2024;31(29):4703-4724. doi: 10.2174/0109298673276076231124104513.
Tuberculosis (TB) remains a primary global health concern, necessitating the discovery and development of new anti-TB drugs, mainly to combat drug-resistant strains. In this context, thiourea derivatives have emerged as promising candidates in TB drug discovery due to their diverse chemical structures and pharmacological properties. This review aimed to explore this potential, identifying and exploring molecular targets for thiourea derivatives in (Mtb) and the potential application of virtual screening techniques in drug discovery. We have compiled a comprehensive list of possible molecular targets of thiourea derivatives in Mtb. The enzymes are primarily involved in the biosynthesis of various cell wall components, including mycolic acids, peptidoglycans, and arabinans, or targets in the branched-chain amino acid biosynthesis (BCAA) pathway and detoxification mechanisms. We discuss the potential of these targets as critical constituents for the design of novel anti-TB drugs. Besides, we highlight the opportunities that virtual screening methodologies present in identifying potential thiourea derivatives that can interact with these molecular targets. The presented findings contribute to the ongoing efforts in TB drug discovery and lay the foundation for further research in designing and developing more effective treatments against this devastating disease.
结核病 (TB) 仍然是一个主要的全球健康关注点，需要发现和开发新的抗结核药物，主要是为了对抗耐药菌株。在这种情况下，由于其多样的化学结构和药理学特性，硫脲衍生物在结核病药物发现中成为有前途的候选物。本综述旨在探讨这种潜力，确定并探索硫脲衍生物在结核分枝杆菌 (Mtb) 中的分子靶点以及虚拟筛选技术在药物发现中的潜在应用。我们已经编制了一份硫脲衍生物在 Mtb 中可能的分子靶点的综合清单。这些酶主要参与各种细胞壁成分的生物合成，包括分枝菌酸、肽聚糖和阿拉伯聚糖，或分支链氨基酸生物合成 (BCAA) 途径和解毒机制中的靶标。我们讨论了这些靶点作为设计新型抗结核药物的关键成分的潜力。此外，我们强调了虚拟筛选方法在识别可能与这些分子靶点相互作用的潜在硫脲衍生物方面提供的机会。提出的发现有助于结核病药物发现的持续努力，并为设计和开发针对这种破坏性疾病的更有效的治疗方法奠定了基础。
