In Vitro and In Silico Antimalarial Evaluation of FM-AZ, a New Artemisinin Derivative

• Published in: Medicines (Basel, Switzerland) Vol. 9; no. 2; p. 8
• Main Authors: Tsamesidis, Ioannis, Mousavizadeh, Farnoush, Egwu, Chinedu O, Amanatidou, Dionysia, Pantaleo, Antonella, Benoit-Vical, Françoise, Reybier, Karine, Giannis, Athanassios
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.01.2022; MDPI
• Subjects: Amino acids; artemisinin resistance; Chemical Sciences; Chromatography; Coordination chemistry; Glucose; Hemoglobin; in silico study; Investigations; LC-MS; Malaria; Mass spectrometry; novel artemisinin derivatives; Oxidative stress; Parasites; Proteins; ROS; Scientific imaging; France; Southeast Asia; novel artemisinin derivatives; artemisinin resistance; in silico study; LC-MS; ROS; Artemisinin resistance; Novel artemisinin derivatives
• ISSN: 2305-6320; 2305-6320
• DOI: 10.3390/medicines9020008

Artemisinin-based Combination Therapies (ACTs) are currently the frontline treatment against malaria, but parasite resistance to artemisinin (ART) and its derivatives, core components of ACTs, is spreading in the Mekong countries. In this study, we report the synthesis of several novel artemisinin derivatives and evaluate their in vitro and in silico capacity to counteract artemisinin resistance. Furthermore, recognizing that the malaria parasite devotes considerable resources to minimizing the oxidative stress that it creates during its rapid consumption of hemoglobin and the release of heme, we sought to explore whether further augmentation of this oxidative toxicity might constitute an important addition to artemisinins. The present report demonstrates, in vitro, that FM-AZ, a newly synthesized artemisinin derivative, has a lower IC than artemisinin in and a rapid action in killing the parasites. The docking studies for important parasite protein targets, PfATP6 and PfHDP, complemented the in vitro results, explaining the superior IC values of FM-AZ in comparison with ART obtained for the ART-resistant strain. However, cross-resistance between FM-AZ and artemisinins was evidenced in vitro.