Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Mecca 24321, Saudi Arabia.
Department of Pharmacy, Abasyn University Peshawar, Khyber Pakhtunkhwa 25000, Pakistan.
Molecules. 2020 Dec 2;25(23):5685. doi: 10.3390/molecules25235685.
According to WHO report, globally about 10 million active tuberculosis cases, resulting in about 1.6 million deaths, further aggravated by drug-resistant tuberculosis and/or comorbidities with HIV and diabetes are present. Incomplete therapeutic regimen, meager dosing, and the capability of the latent and/or active state tubercular bacilli to abide and do survive against contemporary first-line and second line antitubercular drugs escalate the prevalence of drug-resistant tuberculosis. As a better understanding of tuberculosis, microanatomy has discovered an extended range of new promising antitubercular targets and diagnostic biomarkers. However, there are still no new approved antitubercular drugs of routine therapy for several decades, except for bedaquiline, delamanid, and pretomanid approved tentatively. Despite this, innovative methods are also urgently needed to find potential new antitubercular drug candidates, which potentially decimate both latent state and active state . To explore and identify the most potential antitubercular drug candidate among various reported compounds, we focused to highlight the promising lead derivatives of isoniazid, coumarin, griselimycin, and the antimicrobial peptides. The aim of the present review is to fascinate significant lead compounds in the development of potential clinical drug candidates that might be more precise and effective against drug-resistant tuberculosis, the world research looking for a long time.
根据世界卫生组织的报告，全球约有 1000 万例活动性肺结核病例，导致约 160 万人死亡，此外，耐药性肺结核以及/或合并感染 HIV 和糖尿病的情况使形势进一步恶化。治疗方案不完整、用药剂量不足，以及潜伏和/或活动状态的结核杆菌有能力抵抗当代一线和二线抗结核药物，这些因素都导致了耐药性肺结核的流行。随着对肺结核的深入了解，微观解剖学发现了一系列新的有前途的抗结核靶标和诊断生物标志物。然而，除了贝达喹啉、德拉马尼和普托马尼德这三种暂定批准的药物外，几十年来，结核病常规治疗中仍没有新的批准的抗结核药物。尽管如此，仍迫切需要创新方法来寻找有潜力的新的抗结核候选药物，这些药物有可能同时消除潜伏状态和活动状态的结核杆菌。为了在各种已报道的化合物中探索和确定最有潜力的抗结核候选药物，我们重点强调了异烟肼、香豆素、格氏霉素和抗菌肽的有前途的先导衍生物。本综述的目的是强调在开发有潜力的临床候选药物方面的重要先导化合物，这些化合物可能对耐药性肺结核更有效、更精确，这是全球研究长期以来一直在寻找的。
