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 <i>Plasmodium</i> <i>falciparum</i> malaria, but parasite resistance to artemisinin (ART) and its derivatives, core components of ACTs, is spreading in the Mekong countries. In this s...
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MDPI AG
2022-01-01
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| Series: | Medicines |
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| Online Access: | https://www.mdpi.com/2305-6320/9/2/8 |
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| author | Ioannis Tsamesidis Farnoush Mousavizadeh Chinedu O. Egwu Dionysia Amanatidou Antonella Pantaleo Françoise Benoit-Vical Karine Reybier Athanassios Giannis |
| author_facet | Ioannis Tsamesidis Farnoush Mousavizadeh Chinedu O. Egwu Dionysia Amanatidou Antonella Pantaleo Françoise Benoit-Vical Karine Reybier Athanassios Giannis |
| author_sort | Ioannis Tsamesidis |
| collection | DOAJ |
| description | Artemisinin-based Combination Therapies (ACTs) are currently the frontline treatment against <i>Plasmodium</i> <i>falciparum</i> 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 <i>Plasmodium falciparum</i> 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<sub>50</sub> than artemisinin in <i>P. falciparum</i> 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<sub>50</sub> 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. |
| first_indexed | 2024-03-09T21:28:55Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2305-6320 |
| language | English |
| last_indexed | 2024-03-09T21:28:55Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicines |
| spelling | doaj.art-cc061a7a9a3d4a7a9402eafea234359c2023-11-23T21:01:41ZengMDPI AGMedicines2305-63202022-01-0192810.3390/medicines9020008In Vitro and In Silico Antimalarial Evaluation of FM-AZ, a New Artemisinin DerivativeIoannis Tsamesidis0Farnoush Mousavizadeh1Chinedu O. Egwu2Dionysia Amanatidou3Antonella Pantaleo4Françoise Benoit-Vical5Karine Reybier6Athanassios Giannis7UMR 152 Pharma-Dev, Universite de Toulouse III, IRD, UPS, 31400 Toulouse, FranceInstitute for Organic Chemistry, University of Leipzig, Johannisallee 29, 04301 Leipzig, GermanyUMR 152 Pharma-Dev, Universite de Toulouse III, IRD, UPS, 31400 Toulouse, FranceDepartment of Biomedical Sciences, School of Health, International Hellenic University, 57400 Thessaloniki, GreeceDepartment of Biomedical Sciences, University of Sassari, 07100 Sassari, ItalyLaboratoire de Chimie de Coordination, LCC—CNRS, Universite de Toulouse, 31077 Toulouse, FranceUMR 152 Pharma-Dev, Universite de Toulouse III, IRD, UPS, 31400 Toulouse, FranceInstitute for Organic Chemistry, University of Leipzig, Johannisallee 29, 04301 Leipzig, GermanyArtemisinin-based Combination Therapies (ACTs) are currently the frontline treatment against <i>Plasmodium</i> <i>falciparum</i> 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 <i>Plasmodium falciparum</i> 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<sub>50</sub> than artemisinin in <i>P. falciparum</i> 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<sub>50</sub> 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.https://www.mdpi.com/2305-6320/9/2/8novel artemisinin derivativesin silico studyartemisinin resistanceROSLC-MS |
| spellingShingle | Ioannis Tsamesidis Farnoush Mousavizadeh Chinedu O. Egwu Dionysia Amanatidou Antonella Pantaleo Françoise Benoit-Vical Karine Reybier Athanassios Giannis In Vitro and In Silico Antimalarial Evaluation of FM-AZ, a New Artemisinin Derivative Medicines novel artemisinin derivatives in silico study artemisinin resistance ROS LC-MS |
| title | In Vitro and In Silico Antimalarial Evaluation of FM-AZ, a New Artemisinin Derivative |
| title_full | In Vitro and In Silico Antimalarial Evaluation of FM-AZ, a New Artemisinin Derivative |
| title_fullStr | In Vitro and In Silico Antimalarial Evaluation of FM-AZ, a New Artemisinin Derivative |
| title_full_unstemmed | In Vitro and In Silico Antimalarial Evaluation of FM-AZ, a New Artemisinin Derivative |
| title_short | In Vitro and In Silico Antimalarial Evaluation of FM-AZ, a New Artemisinin Derivative |
| title_sort | in vitro and in silico antimalarial evaluation of fm az a new artemisinin derivative |
| topic | novel artemisinin derivatives in silico study artemisinin resistance ROS LC-MS |
| url | https://www.mdpi.com/2305-6320/9/2/8 |
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