In Vitro and In Silico Antimalarial Evaluation of FM-AZ, a New Artemisinin Derivative - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Medicines Année : 2022

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

Résumé

Artemisinin-based Combination Therapies (ACTs) are currently the frontline treatment against Plasmodium falciparum 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 Plasmodium falciparum 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 IC50 than artemisinin in P. falciparum 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 IC50 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.
Fichier principal
Vignette du fichier
Tsamesidis, In vitro and in silico antimalarial evaluation, 2022.pdf (1.4 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03660647 , version 1 (06-05-2022)

Licence

Paternité

Identifiants

Citer

Ioannis Tsamesidis, Farnoush Mousavizadeh, Chinedu Egwu, Dionysia Amanatidou, Antonella Pantaleo, et al.. In Vitro and In Silico Antimalarial Evaluation of FM-AZ, a New Artemisinin Derivative. Medicines, 2022, 9 (2), pp.8. ⟨10.3390/medicines9020008⟩. ⟨hal-03660647⟩
30 Consultations
18 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More