Singh Vinayak, Mambwe Dickson, Korkor Constance Mawunyo, Chibale Kelly
Drug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch 7701, South Africa.
South African Medical Research Council Drug Discovery and Development Research Unit, Department of Chemistry and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa.
ACS Med Chem Lett. 2022 Jul 11;13(8):1221-1230. doi: 10.1021/acsmedchemlett.2c00142. eCollection 2022 Aug 11.
As the so-called "next frontier" in global economic terms, Africa's disease burden continues to choke and cripple economic growth across the continent. The highest burden is attributable to malaria and tuberculosis (TB), which also remain among the deadliest infectious diseases affecting mankind the world over (Malaria, 627,000 deaths; TB, 1.5 million deaths, in 2020). In achieving self-determination with respect to the health needs of all who live on the continent, Africa must align with global north efforts and be a source of health innovation. This will in part require the creation of an ecosystem of innovative pharmaceutical R&D and expanding it across the continent by scaling up through sustained performance and excellence. To this end, the Holistic Drug Discovery and Development (H3D) Centre at University of Cape Town in South Africa has risen to this challenge. Here, we highlight the innovation experiences gained at H3D, covering the advances made in our quest to contribute to a global pipeline of therapeutic interventions against malaria and TB. We discuss selected chemical series starting from their identification, structure-activity relationships, mode of action, safety, proof-of-concept studies, and lessons learned.
作为全球经济领域所谓的“下一个前沿阵地”，非洲的疾病负担继续阻碍并削弱着整个大陆的经济增长。最大的负担归因于疟疾和结核病（TB），它们仍是全球影响人类的最致命传染病（2020年，疟疾导致62.7万人死亡；结核病导致150万人死亡）。为了实现满足非洲大陆所有居民健康需求的自主发展，非洲必须与北半球国家共同努力，并成为健康创新的源泉。这在一定程度上需要创建一个创新药物研发生态系统，并通过持续的卓越表现和扩大规模，在整个非洲大陆推广。为此，南非开普敦大学的整体药物发现与开发（H3D）中心迎接了这一挑战。在此，我们重点介绍在H3D获得的创新经验，涵盖我们在为全球疟疾和结核病治疗干预药物研发做出贡献的过程中取得的进展。我们讨论选定的化学系列，从它们的识别、构效关系、作用方式、安全性、概念验证研究以及吸取的经验教训说起。
