Pepe Dionissia A, Toumpa Dimitra, André-Barrès Christiane, Menendez Christophe, Mouray Elisabeth, Baltas Michel, Grellier Philippe, Papaioannou Dionissios, Athanassopoulos Constantinos M
Synthetic Organic Chemistry Laboratory, Department of Chemistry, University of Patras, Patras GR-26504, Greece.
LSPCMIB, UMR-CNRS 5068, Université Paul Sabatier-Toulouse III, 118 route de Narbonne, Toulouse CEDEX 9 31062, France.
ACS Med Chem Lett. 2020 Mar 24;11(5):921-927. doi: 10.1021/acsmedchemlett.9b00669. eCollection 2020 May 14.
A series of novel hybrids of artemisinin (ART) with either a phytormone endoperoxide G factor analogue (GMeP) or chloroquine (CQ) and conjugates of the same compounds with the polyamines (PAs), spermidine (Spd), and homospermidine (Hsd) were synthesized and their antiplasmodial activity was evaluated using the CQ-resistant FcB1/Colombia strain. The ART-GMeP hybrid and compounds and which are conjugates of Spd and Hsd with two molecules of ART and one molecule of GMeP, were the most potent with IC values of 2.6, 8.4, and 10.6 nM, respectively. The same compounds also presented the highest selectivity indexes against the primary human fibroblast cell line AB943 ranging from 16 372 for the hybrid to 983 for the conjugate of Hsd.
合成了一系列青蒿素（ART）与植物激素内过氧化物G因子类似物（GMeP）或氯喹（CQ）的新型杂化物，以及这些化合物与多胺（PAs）、亚精胺（Spd）和高亚精胺（Hsd）的缀合物，并使用抗氯喹的FcB1/哥伦比亚菌株评估了它们的抗疟活性。ART-GMeP杂化物以及Spd和Hsd与两分子ART和一分子GMeP的缀合物化合物活性最强，IC值分别为2.6、8.4和10.6 nM。相同的化合物对原代人成纤维细胞系AB943也表现出最高的选择性指数，从杂化物的16372到Hsd缀合物的983不等。
