新型福司米霉素衍生物与青蒿素和氨基氯喹的缀合物的合成及抗疟活性。

Synthesis and Antiplasmodial Activity of Novel Fosmidomycin Derivatives and Conjugates with Artemisinin and Aminochloroquinoline.

机构信息

Synthetic Organic Chemistry Laboratory, Department of Chemistry, University of Patras, GR-26504 Patras, Greece.

LSPCMIB, UMR-CNRS 5068, Université Paul Sabatier-Toulouse III, CEDEX 9, 31062 Toulouse, France.

出版信息

Molecules. 2020 Oct 21;25(20):4858. doi: 10.3390/molecules25204858.

Malaria, despite many efforts, remains among the most problematic infectious diseases worldwide, mainly due to the development of drug resistance by The antibiotic fosmidomycin (FSM) is also known for its antimalarial activity by targeting the non-mevalonate isoprenoid synthesis pathway, which is essential for the malaria parasites but is absent in mammalians. In this study, we synthesized and evaluated against the chloroquine-resistant strain, a series of FSM analogs, derivatives, and conjugates with other antimalarial agents, such as artemisinin (ART) and aminochloroquinoline (ACQ). The biological evaluation revealed four new compounds with higher antimalarial activity than FSM: two FSM-ACQ derivatives and two FSM-ART conjugates, with 3.5-5.4 and 41.5-23.1 times more potent activities than FSM, respectively.

疟疾尽管经过了许多努力，仍然是全球最成问题的传染病之一，主要是由于抗生素福米霉素（FSM）的耐药性发展。福米霉素也因其靶向非甲羟戊酸异戊烯醇合成途径的抗疟活性而闻名，该途径对疟原虫至关重要，但在哺乳动物中不存在。在这项研究中，我们合成并评估了一系列针对氯喹耐药株的 FSM 类似物、衍生物和与其他抗疟药物（如青蒿素（ART）和氨基氯喹啉（ACQ））的缀合物。生物评价显示，有四个新化合物比 FSM 具有更高的抗疟活性：两个 FSM-ACQ 衍生物和两个 FSM-ART 缀合物，其活性分别比 FSM 强 3.5-5.4 倍和 41.5-23.1 倍。