Njogu Peter M, Guantai Eric M, Pavadai Elumalai, Chibale Kelly
Department of Pharmaceutical Chemistry and ‡Division of Pharmacology, School of Pharmacy, University of Nairobi , P.O. Box 19676-00202, Nairobi, Kenya.
Department of Chemistry, ⊗Institute of Infectious Disease and Molecular Medicine, and ΘSouth African Medical Research Council Drug Discovery and Development Research Unit, University of Cape Town , Rondebosch 7701, South Africa.
ACS Infect Dis. 2016 Jan 8;2(1):8-31. doi: 10.1021/acsinfecdis.5b00093. Epub 2015 Nov 16.
Despite the tremendous improvement in overall global health heralded by the adoption of the Millennium Declaration in the year 2000, tropical infections remain a major health problem in the developing world. Recent estimates indicate that the major tropical infectious diseases, namely, malaria, tuberculosis, trypanosomiasis, and leishmaniasis, account for more than 2.2 million deaths and a loss of approximately 85 million disability-adjusted life years annually. The crucial role of chemotherapy in curtailing the deleterious health and economic impacts of these infections has invigorated the search for new drugs against tropical infectious diseases. The research efforts have involved increased application of computational technologies in mainstream drug discovery programs at the hit identification, hit-to-lead, and lead optimization stages. This review highlights various computer-aided drug discovery approaches that have been utilized in efforts to identify novel antimalarial, antitubercular, antitrypanosomal, and antileishmanial agents. The focus is largely on developments over the past 5 years (2010-2014).
尽管2000年《千年宣言》的通过预示着全球总体健康状况有了巨大改善,但热带感染仍是发展中世界的一个主要健康问题。最近的估计表明,主要的热带传染病,即疟疾、结核病、锥虫病和利什曼病,每年导致超过220万人死亡,约8500万伤残调整生命年的损失。化疗在减少这些感染对健康和经济的有害影响方面的关键作用,激发了人们对治疗热带传染病新药的探索。这些研究工作包括在主流药物发现项目的活性化合物识别、活性化合物到先导化合物以及先导化合物优化阶段更多地应用计算技术。本综述重点介绍了为识别新型抗疟、抗结核、抗锥虫和抗利什曼原虫药物所采用的各种计算机辅助药物发现方法。重点主要放在过去5年(2010 - 2014年)的进展上。