College of Life Sciences, Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun, Jilin, China.
Shandong Key Laboratory of Biophysics, Institute of Biophysics, Dezhou University, Dezhou, Shandong, China.
Arch Pharm (Weinheim). 2022 Jul;355(7):e2200077. doi: 10.1002/ardp.202200077. Epub 2022 Apr 6.
Malaria, a mosquito-borne parasitic infection caused by protozoan parasites belonging to the genus Plasmodium, is a dangerous disease that contributes to millions of hospital visits and hundreds and thousands of deaths across the world, especially in Sub-Saharan Africa. Antimalarial agents are vital for treating malaria and controlling transmission, and 1,2,4-trioxolane/trioxane-containing agents, especially artemisinin and its derivatives, own antimalarial efficacy and low toxicity with unique mechanisms of action. Moreover, artemisinin-based combination therapies were recommended by the World Health Organization as the first-line treatment for uncomplicated malaria infection and have remained as the mainstay of the treatment of malaria, demonstrating that 1,2,4-trioxolane/trioxane derivatives are useful prototypes for the control and eradication of malaria. However, malaria parasites have already developed resistance to almost all of the currently available antimalarial agents, creating an urgent need for the search of novel pharmaceutical interventions for malaria. The purpose of this review article is to provide an emphasis on the current scenario (January 2012 to January 2022) of 1,2,4-trioxolane/trioxane hybrids and dimers with potential antimalarial activity and the structure-activity relationships are also discussed to facilitate further rational design of more effective candidates.
疟疾是一种由疟原虫属原生动物寄生虫引起的蚊媒寄生虫感染，是一种危险的疾病，在全世界导致数百万人住院治疗和数千人死亡，特别是在撒哈拉以南非洲。抗疟药物对于治疗疟疾和控制传播至关重要，1,2,4-三恶烷/三恶烷类药物，特别是青蒿素及其衍生物，具有独特的作用机制，具有抗疟疗效和低毒性。此外，世界卫生组织推荐青蒿素为治疗无并发症疟疾感染的一线治疗药物，一直是治疗疟疾的主要药物，这表明 1,2,4-三恶烷/三恶烷衍生物是控制和消灭疟疾的有用原型。然而，疟原虫已经对几乎所有现有的抗疟药物产生了耐药性，这就迫切需要寻找新的抗疟药物干预措施。本文的目的是强调 1,2,4-三恶烷/三恶烷类化合物及其具有潜在抗疟活性的二聚体的最新研究进展（2012 年 1 月至 2022 年 1 月），并讨论结构-活性关系，以促进更有效候选药物的进一步合理设计。
