Zlotos Darius P, Franke Siegrid, Ngwa Che J, Reiss Timo, Weinmann Joshua, Pradel Gabriele, Przyborski Jude M, Holzgrabe Ulrike
Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, The German University in Cairo New Cairo City 11835 Cairo Egypt
Biochemistry and Molecular Biology, Interdisciplinary Research Center, Justus Liebig University Giessen Heinrich-Buff-Ring 26-32 35392 Giessen Germany.
RSC Med Chem. 2025 Apr 11. doi: 10.1039/d4md01026d.
The synthesis of pentacyclic 6,13-pyrazino[1,2-;4,5-']diindole analogues and their evaluation for antiplasmodial activity against 3D7 strains using [H]hypoxanthine incorporation and SYBR® Green assays are reported. While the unsubstituted analogues are characterized by only weak antimalarial activity, introduction of one or two basic side-chains led to substantially increased antiplasmodial activity and reduced cytotoxicity against macrophage J774.1 cells. Screening data on chloroquine-sensitive 3D7 and chloroquine-resistant Dd2 strains using the Malstat assay showed that compounds 18, 21 and 23 are characterized by nanomolar activity against both strains, making them promising leads for the development of new antimalarial agents against chloroquine-resistant .
报道了五环6,13-吡嗪并[1,2-;4,5-']二吲哚类似物的合成及其使用[H]次黄嘌呤掺入法和SYBR® Green分析法对3D7菌株抗疟活性的评估。虽然未取代的类似物仅表现出较弱的抗疟活性，但引入一个或两个碱性侧链会导致抗疟活性大幅增加，并降低对巨噬细胞J774.1细胞的细胞毒性。使用Malstat分析法对氯喹敏感的3D7和氯喹抗性的Dd2菌株的筛选数据表明，化合物18、21和23对这两种菌株均具有纳摩尔活性，使其成为开发抗氯喹抗性新型抗疟药物的有前景的先导化合物。
