{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T15:31:29Z","timestamp":1777044689962,"version":"3.51.4"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicines"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/medicines9020008","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T20:40:18Z","timestamp":1643143218000},"page":"8","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["In Vitro and In Silico Antimalarial Evaluation of FM-AZ, a New Artemisinin Derivative"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1439-3920","authenticated-orcid":false,"given":"Ioannis","family":"Tsamesidis","sequence":"first","affiliation":[{"name":"UMR 152 Pharma-Dev, Universite de Toulouse III, IRD, UPS, 31400 Toulouse, France"},{"name":"Department of Biomedical Sciences, School of Health, International Hellenic University, 57400 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farnoush","family":"Mousavizadeh","sequence":"additional","affiliation":[{"name":"Institute for Organic Chemistry, University of Leipzig, Johannisallee 29, 04301 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3408-5471","authenticated-orcid":false,"given":"Chinedu","family":"Egwu","sequence":"additional","affiliation":[{"name":"UMR 152 Pharma-Dev, Universite de Toulouse III, IRD, UPS, 31400 Toulouse, France"},{"name":"Medical Biochemistry, College of Medicine, Alex-Ekwueme Federal University, Ndufu-Alike Ikwo, P.M.B. 1010, Abakaliki 482131, Nigeria"},{"name":"Laboratoire de Chimie de Coordination, LCC\u2014CNRS, Universite de Toulouse, 31077 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5849-4192","authenticated-orcid":false,"given":"Dionysia","family":"Amanatidou","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Health, International Hellenic University, 57400 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2954-7053","authenticated-orcid":false,"given":"Antonella","family":"Pantaleo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7oise","family":"Benoit-Vical","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie de Coordination, LCC\u2014CNRS, Universite de Toulouse, 31077 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karine","family":"Reybier","sequence":"additional","affiliation":[{"name":"UMR 152 Pharma-Dev, Universite de Toulouse III, IRD, UPS, 31400 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2203-0959","authenticated-orcid":false,"given":"Athanassios","family":"Giannis","sequence":"additional","affiliation":[{"name":"Institute for Organic Chemistry, University of Leipzig, Johannisallee 29, 04301 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10210","DOI":"10.1002\/anie.201601967","article-title":"Artemisinin\u2014A Gift from Traditional Chinese Medicine to the World (Nobel Lecture)","volume":"55","author":"Tu","year":"2016","journal-title":"Angew. 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