Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 UM-CNRS-ENSCM , Université Montpellier, Equipe Nucléosides & Effecteurs Phosphorylés , Place E. Bataillon, cc 1704 , 34095 Montpellier , France.
Dynamique des Interactions Membranaires Normales et Pathologiques (DIMNP), UMR 5235 UM-CNRS , Université Montpellier , Place E. Bataillon , 34095 Montpellier , France.
J Med Chem. 2019 Sep 26;62(18):8365-8391. doi: 10.1021/acs.jmedchem.9b00182. Epub 2019 Apr 25.
Malaria still affects around 200 million people and is responsible for more than 400,000 deaths per year, mostly children in subequatorial areas. This disease is caused by parasites of the genus. Only a few WHO-recommended treatments are available to prevent or cure plasmodial infections, but genetic mutations in the causal parasites have led to onset of resistance against all commercial antimalarial drugs. New drugs and targets are being investigated to cope with this emerging problem, including enzymes belonging to the main metabolic pathways, while nucleoside and nucleotide analogues are also a promising class of potential drugs. This review highlights the main metabolic pathways targeted for the development of potential antiplasmodial therapies based on nucleos(t)ide analogues, as well as the different series of purine-containing nucleoside and nucleotide derivatives designed to inhibit purine metabolism.
疟疾仍影响着约 2 亿人，每年导致超过 40 万人死亡，大多数是赤道地区的儿童。这种疾病是由属的寄生虫引起的。目前只有少数世界卫生组织推荐的治疗方法可用于预防或治疗疟原虫感染，但寄生虫的基因突变导致对所有商业抗疟药物产生抗药性。为了应对这一新出现的问题，人们正在研究新的药物和靶点，包括属于主要代谢途径的酶，而核苷和核苷酸类似物也是一类有前途的潜在药物。这篇综述重点介绍了基于核苷类似物开发潜在抗疟疗法的主要代谢途径，以及为抑制嘌呤代谢而设计的不同系列含嘌呤核苷和核苷酸衍生物。
