环肽类化合物的抗结核活性

Cyclopeptide Derivatives with Anti-tubercular Potential

结核病主要是由结核分枝杆菌引起的慢性传染性疾病,具有高发病率和高死亡率等特点。近年来,耐药结核病的发病率呈逐年递增之势,导致现有抗结核药物的疗效不断下降。因此,亟须开发新型抗结核药物。环肽类化合物具有易于合成、代谢稳定性强、毒副作用低和口服利用度高等优点,且已有数十种环肽类药物用于临床治疗各种疾病。值得一提的是,环肽类化合物如Cyclomarin A和Lassomycin等可作用于结核分枝杆菌的酪蛋白水解蛋白酶C1,对包括耐多药和广泛耐药结核分枝杆菌在内的多种耐药结核分枝杆菌显示出良好的活性。因此,环肽类化合物在抗结核领域引起了药物化学家的广泛关注。本文将着重介绍近五年(2018年1月—2023年1月)所开发的具有抗结核活性的环肽类化合物的最新研究进展,为进一步研究提供参考。

Mycobacterium tuberculosis is the primary cause of tuberculosis,a chronic infectious disease with a high incidence and fatality rate.The incidence rate of drug-resistant tuberculosis is increasing year by year,leading to the decline of the efficacy of existing anti-tubercular drugs.Therefore,it is urgent to develop new antitubercular drugs.Cyclopeptide derivatives have the advantages of feasible synthesis,good metabolic stability,low toxicity,and side effects,and high oral availability,and dozens of cyclopeptides have been used for various diseases in clinics.It is important to note that cyclopeptide derivatives,including Cyclomarin A and Lassomycin,can affect Mycobacterium tuberculosis'caseinolytic protease Cl and,as a result,have excellent activity against different drugresistant Mycobacterium tuberculosis strains,including extensively drug-resistant and multidrug-resistant varieties.Therefore,cyclopeptide derivatives have attracted great attention in seeking novel anti-tubercular agents.This review will concentrate on the most recent advancements in the study of cyclopeptide derivatives with anti-tubercular activity created in the last five years,serving as a guide for future study.