Quan Diana, Nagalingam Gayathri, Payne Richard, Triccas James A
Microbial Pathogenesis and Immunity Group, Department of Infectious Diseases and Immunology, Sydney Medical School, The University of Sydney, NSW, Australia; Tuberculosis Research Program, Centenary Institute, The University of Sydney, NSW, Australia.
School of Chemistry, The University of Sydney, Sydney, NSW, Australia.
Int J Infect Dis. 2017 Mar;56:212-220. doi: 10.1016/j.ijid.2016.12.024. Epub 2017 Jan 3.
Tuberculosis (TB) continues to be a significant cause of mortality and morbidity worldwide. An estimated 2 billion individuals are infected with Mycobacterium tuberculosis and annually there are approximately 10 million new cases of clinical TB and 1.5 million deaths. Currently available drugs and vaccines have had no significant impact on TB control. In addition, the emergence of drug resistant TB is considered a public health crisis, with some strains now resistant to all available drugs. Unfortunately, the growing burden of antibiotic resistance is coupled with decreased effort in the development of new antibiotics. Natural sources are attractive starting points in the search for anti-tubercular drugs because they are extremely rich in chemical diversity and have privileged antimicrobial activity. This review will discuss recent advances in the development of TB drug leads from natural products, with a particular focus on anti-mycobacterial compounds in late-stage preclinical and clinical development.
结核病(TB)仍然是全球范围内导致死亡和发病的重要原因。据估计,有20亿人感染了结核分枝杆菌,每年约有1000万新的临床结核病病例,150万人死亡。目前可用的药物和疫苗对结核病控制没有显著影响。此外,耐药结核病的出现被视为一场公共卫生危机,现在有些菌株对所有可用药物都具有耐药性。不幸的是,抗生素耐药性负担日益加重,与此同时新抗生素研发的投入却在减少。天然来源因其具有极其丰富的化学多样性和独特的抗菌活性,是寻找抗结核药物颇具吸引力的起始点。本综述将讨论天然产物来源的结核病药物先导物开发的最新进展,特别关注处于临床前后期和临床开发阶段的抗分枝杆菌化合物。