Synthesis of Novel G Factor or Chloroquine-Artemisinin Hybrids and Conjugates with Potent Antiplasmodial Activity

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2020 May 22

PMID 32435406

Citations 8

Authors

Dionissia A Pepe

Dimitra Toumpa

Christiane Andre-Barres

Christophe Menendez

Elisabeth Mouray

Michel Baltas

Philippe Grellier

Dionissios Papaioannou

Constantinos M Athanassopoulos

Affiliations

Soon will be listed here.

Abstract

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.

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