Department of Chemistry, A.P.S.M. College, Barauni (A Constituent Unit of Lalit Narayan Mithila University, Darbhanga), Begusarai, 851112, Bihar, India.
Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, India.
Eur J Med Chem. 2022 Aug 5;238:114454. doi: 10.1016/j.ejmech.2022.114454. Epub 2022 May 13.
Tuberculosis, a disease of poverty is a communicable infection with a reasonably high mortality rate worldwide. 10 Million new cases of TB were reported with approx 1.4 million deaths in the year 2019. Due to the growing number of drug-sensitive and drug-resistant tuberculosis cases, there is a vital need to develop new and effective candidates useful to combat this deadly disease. Despite tremendous efforts to identify a mechanism-based novel antitubercular agent, only a few have entered into clinical trials in the last six decades. In recent years, triazoles have been well explored as the most valuable scaffolds in drug discovery and development. Triazole framework possesses favorable properties like hydrogen bonding, moderate dipole moment, enhanced water solubility, and also the ability to bind effectively with biomolecular targets of M. tuberculosis and therefore this scaffold displayed excellent potency against TB. This review is an endeavor to summarize an up-to-date innovation of triazole-appended hybrids during the last 10 years having potential in vitro and in vivo antitubercular activity with structure activity relationship analysis. This review may help medicinal chemists to explore the triazole scaffolds for the rational design of potent drug candidates having better efficacy, improved selectivity and minimal toxicity so that these hybrid NCEs can effectively be explored as potential lead to fight against M. tuberculosis.
结核病是一种贫困病,是一种具有相当高全球死亡率的传染性感染。2019 年报告了 1000 万例新的结核病病例,约有 140 万人死亡。由于越来越多的药物敏感和耐药结核病病例,迫切需要开发新的和有效的候选药物来对抗这种致命疾病。尽管为了确定基于机制的新型抗结核药物做出了巨大努力,但在过去六十年中,只有少数几种药物进入了临床试验。近年来,三唑类化合物作为药物发现和开发中最有价值的支架得到了广泛的研究。三唑骨架具有良好的性质,如氢键、适中的偶极矩、增强的水溶性,以及与结核分枝杆菌生物分子靶标有效结合的能力,因此该支架对结核病具有优异的活性。本综述旨在总结过去 10 年中三唑类化合物的最新研究进展,这些化合物具有潜在的体外和体内抗结核活性,并进行了构效关系分析。本综述可能有助于药物化学家探索三唑类化合物,以合理设计具有更好疗效、更高选择性和更低毒性的有效药物候选物,以便这些新型化学实体能够有效地作为潜在的抗结核药物进行探索。