{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:57:04Z","timestamp":1792007824596,"version":"4.4.0"},"reference-count":34,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T00:00:00Z","timestamp":1733529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"DGA (Direction G\u00e9n\u00e9rale de l\u2019Armement, Minist\u00e8re de la D\u00e9fense, France)","doi-asserted-by":"publisher","award":["ANR-12-STR-003"],"award-info":[{"award-number":["ANR-12-STR-003"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Currently, artemisinin-based combination therapy is recommended as first-line treatment of uncomplicated falciparum malaria. Arylamino alcohols (AAAs) such as mefloquine (MQ) are the preferred partner drugs due to their longer half-life, reliable absorption and strong antimalarial activity. However, the mode of action of MQ remains poorly understood and its neurotoxicity limits its use. Furthermore, the emergence of drug-resistant parasites requires development of new antimalarial drugs. The aim of this study was to evaluate the \u03b2-hematin inhibition capacity of three pairs of enantiopure AAAs 1\u20133 (a\/S and b\/R) derived from MQ or enpiroline (ENP), a pyridine-based MQ analog with strong antimalarial activity. Inhibition of \u03b2-hematin\u2014the synthetic counterpart of hemozoin formation\u2014was determined for each compound. Antimalarial activity against W2 and 3D7 Plasmodium falciparum strains as well as percentages of inhibition of \u03b2-hematin formation were compared to those of reference molecules, i.e., chloroquine (CQ), MQ and ENP. Furthermore, a cytotoxicity study on the human-derived hepatocarcinoma cell line HepG2 was performed. With high antimalarial activity, stronger ability to inhibit \u03b2-hematin formation and low cytotoxicity, AAAs 1a-b and 2a are the most promising. These findings provide a better understanding of their potential mechanisms of action and may pave the way toward developing new lead compounds.<\/jats:p>","DOI":"10.3390\/microorganisms12122524","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T06:16:14Z","timestamp":1733724974000},"page":"2524","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evaluation of In Vitro Inhibition of \u03b2-Hematin Formation: A Step Towards a Comprehensive Understanding of the Mechanism of Action of New Arylamino Alcohols"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3532-6775","authenticated-orcid":false,"given":"C\u00e9line","family":"Damiani","sequence":"first","affiliation":[{"name":"Agents Infectieux, R\u00e9sistance et Chimioth\u00e9rapie (AGIR), UR 4294, Universit\u00e9 de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France"},{"name":"Laboratoire de Parasitologie et Mycologie, Centre de Biologie Humaine, CHU Amiens-Picardie, 1 Rond-Point du Pr Cabrol, 80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floriane","family":"Soler","sequence":"additional","affiliation":[{"name":"Laboratoire de Parasitologie et Mycologie, Centre de Biologie Humaine, CHU Amiens-Picardie, 1 Rond-Point du Pr Cabrol, 80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7686-4612","authenticated-orcid":false,"given":"Yohann","family":"Le Govic","sequence":"additional","affiliation":[{"name":"Agents Infectieux, R\u00e9sistance et Chimioth\u00e9rapie (AGIR), UR 4294, Universit\u00e9 de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France"},{"name":"Laboratoire de Parasitologie et Mycologie, Centre de Biologie Humaine, CHU Amiens-Picardie, 1 Rond-Point du Pr Cabrol, 80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9784-575X","authenticated-orcid":false,"given":"Anne","family":"Totet","sequence":"additional","affiliation":[{"name":"Agents Infectieux, R\u00e9sistance et Chimioth\u00e9rapie (AGIR), UR 4294, Universit\u00e9 de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France"},{"name":"Laboratoire de Parasitologie et Mycologie, Centre de Biologie Humaine, CHU Amiens-Picardie, 1 Rond-Point du Pr Cabrol, 80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Bentzinger","sequence":"additional","affiliation":[{"name":"Agents Infectieux, R\u00e9sistance et Chimioth\u00e9rapie (AGIR), UR 4294, Universit\u00e9 de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Bouchut","sequence":"additional","affiliation":[{"name":"Agents Infectieux, R\u00e9sistance et Chimioth\u00e9rapie (AGIR), UR 4294, Universit\u00e9 de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Musti\u00e8re","sequence":"additional","affiliation":[{"name":"Agents Infectieux, R\u00e9sistance et Chimioth\u00e9rapie (AGIR), UR 4294, Universit\u00e9 de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Agnamey","sequence":"additional","affiliation":[{"name":"Agents Infectieux, R\u00e9sistance et Chimioth\u00e9rapie (AGIR), UR 4294, Universit\u00e9 de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2891-9102","authenticated-orcid":false,"given":"Alexandra","family":"Dassonville-Klimpt","sequence":"additional","affiliation":[{"name":"Agents Infectieux, R\u00e9sistance et Chimioth\u00e9rapie (AGIR), UR 4294, Universit\u00e9 de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0118-9151","authenticated-orcid":false,"given":"Pascal","family":"Sonnet","sequence":"additional","affiliation":[{"name":"Agents Infectieux, R\u00e9sistance et Chimioth\u00e9rapie (AGIR), UR 4294, Universit\u00e9 de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,7]]},"reference":[{"key":"ref_1","unstructured":"(2024, October 28). 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