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

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 d...

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Published inMedicines (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
LanguageEnglish
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
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Abstract 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.
AbstractList 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.
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.
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.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.
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.
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 IC 50 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 IC 50 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.
Author Amanatidou, Dionysia
Pantaleo, Antonella
Benoit-Vical, Françoise
Mousavizadeh, Farnoush
Giannis, Athanassios
Reybier, Karine
Egwu, Chinedu O
Tsamesidis, Ioannis
AuthorAffiliation 5 Laboratoire de Chimie de Coordination, LCC—CNRS, Universite de Toulouse, 31077 Toulouse, France; francoise.benoit-vical@lcc-toulouse.fr
3 Institute for Organic Chemistry, University of Leipzig, Johannisallee 29, 04301 Leipzig, Germany; seyedehfarnoush.mousavizadeh@uni-leipzig.de
2 Department of Biomedical Sciences, School of Health, International Hellenic University, 57400 Thessaloniki, Greece; dionusiaam@gmail.com
4 Medical Biochemistry, College of Medicine, Alex-Ekwueme Federal University, Ndufu-Alike Ikwo, P.M.B. 1010, Abakaliki 482131, Nigeria
6 Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy; apantaleo@uniss.it
1 UMR 152 Pharma-Dev, Universite de Toulouse III, IRD, UPS, 31400 Toulouse, France; echojay2010@yahoo.com (C.O.E.); karine.reybier-vuattoux@univ-tlse3.fr (K.R.)
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Keywords novel artemisinin derivatives
artemisinin resistance
in silico study
LC-MS
ROS
Artemisinin resistance
Novel artemisinin derivatives
Language English
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These authors contributed equally to the work.
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Snippet Artemisinin-based Combination Therapies (ACTs) are currently the frontline treatment against malaria, but parasite resistance to artemisinin (ART) and its...
Artemisinin-based Combination Therapies (ACTs) are currently the frontline treatment against Plasmodium falciparum malaria, but parasite resistance to...
Artemisinin-based Combination Therapies (ACTs) are currently the frontline treatment against Plasmodium falciparum malaria, but parasite resistance to...
Artemisinin-based Combination Therapies (ACTs) are currently the frontline treatment against Plasmodium   falciparum malaria, but parasite resistance to...
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StartPage 8
SubjectTerms 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
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Title In Vitro and In Silico Antimalarial Evaluation of FM-AZ, a New Artemisinin Derivative
URI https://www.ncbi.nlm.nih.gov/pubmed/35200752
https://www.proquest.com/docview/2632959733
https://www.proquest.com/docview/2632803700/abstract/
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https://pubmed.ncbi.nlm.nih.gov/PMC8880451
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