{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:48:23Z","timestamp":1792806503102,"version":"4.5.0"},"reference-count":36,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T00:00:00Z","timestamp":1741996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science Fund of the Republic of Serbia, 7328, Reinvention of the diagnostic algorithm and treatment options for reactivated toxoplasmosis\u2014ToxoReTREAT","award":["451-03-136\/2025-03\/200015"],"award-info":[{"award-number":["451-03-136\/2025-03\/200015"]}],"id":[{"id":"https:\/\/ror.org\/02r531a15","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Science Fund of the Republic of Serbia, 7328, Reinvention of the diagnostic algorithm and treatment options for reactivated toxoplasmosis\u2014ToxoReTREAT","award":["451-03-136\/2025-03\/200161"],"award-info":[{"award-number":["451-03-136\/2025-03\/200161"]}],"id":[{"id":"https:\/\/ror.org\/02r531a15","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Science Fund of the Republic of Serbia, 7328, Reinvention of the diagnostic algorithm and treatment options for reactivated toxoplasmosis\u2014ToxoReTREAT","award":["451-03-137\/2025-03\/200161"],"award-info":[{"award-number":["451-03-137\/2025-03\/200161"]}],"id":[{"id":"https:\/\/ror.org\/02r531a15","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ministry of Science, Technological Development, and Innovation of the Republic of Serbia","award":["451-03-136\/2025-03\/200015"],"award-info":[{"award-number":["451-03-136\/2025-03\/200015"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ministry of Science, Technological Development, and Innovation of the Republic of Serbia","award":["451-03-136\/2025-03\/200161"],"award-info":[{"award-number":["451-03-136\/2025-03\/200161"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ministry of Science, Technological Development, and Innovation of the Republic of Serbia","award":["451-03-137\/2025-03\/200161"],"award-info":[{"award-number":["451-03-137\/2025-03\/200161"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ministry of Science, Technological Development, and Innovation of the Republic of Serbia","award":["451-03-136\/2025-03\/200015"],"award-info":[{"award-number":["451-03-136\/2025-03\/200015"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ministry of Science, Technological Development, and Innovation of the Republic of Serbia","award":["451-03-136\/2025-03\/200161"],"award-info":[{"award-number":["451-03-136\/2025-03\/200161"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ministry of Science, Technological Development, and Innovation of the Republic of Serbia","award":["451-03-137\/2025-03\/200161"],"award-info":[{"award-number":["451-03-137\/2025-03\/200161"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Acridine, an aromatic heterocyclic compound, serves as a basis for the synthesis of potent bioactive derivatives, displaying a broad spectrum of biological activity, such as antibacterial, antitumor, and antiparasitic activity. With the ability to undergo various types of electrophilic substitutions, introducing different side chains could lead to compounds being active towards various and potentially multiple biotargets. Toxoplasma gondii, a ubiquitous protozoan parasite with worldwide distribution, poses a major health threat, particularly in immunocompromised patients and fetuses. Current treatment options for toxoplasmosis are scarce, with notable limitations, especially regarding side myelotoxicity and inactivity towards T. gondii cysts, causing a need for novel drug candidates. The aim of this study was to evaluate selected N-(9-acrydinil) amino acid derivatives as potential anti-T. gondii agents. Methods: Synthesis of new derivatives was performed using a two-step method, with the initial mixing of 9-chloroacridine with methanol and sodium alkoxide solution and subsequent adding of appropriate amino acids. Cytotoxicity of the tested compounds was evaluated on the Vero cell line using a MTT assay, while their anti-T. gondii activity was investigated using T. gondii RH strain tachyzoites. Results: CC50 values of the derivatives ranged from 41.72 to 154.10 \u00b5M. Anti-T. gondii activity, displayed as a reduction in the number of viable tachyzoites compared to the untreated control, ranged from 0 to 33.3%. One of the derivatives displayed activity comparable to the standard treatment option while retaining acceptable cytotoxicity. Esterification, presence of aromatic substituents and the length of the amino acid side chain were identified as key factors that affect both toxicity and activity of these derivatives. Conclusions: Promising results obtained throughout this study provide guidelines for further structural modifications of N-(9-acrydinil) amino acid derivatives in order to synthesize drug candidates competitive to standard treatment options for toxoplasmosis.<\/jats:p>","DOI":"10.3390\/pharmaceutics17030374","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T07:49:57Z","timestamp":1742197797000},"page":"374","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["N-(9-Acridinyl) Amino Acid Derivatives: Synthesis and In Vitro Evaluation of Anti-Toxoplasma\u00a0gondii Activity"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9735-3191","authenticated-orcid":false,"given":"\u0110or\u0111e","family":"Zlatkovi\u0107","sequence":"first","affiliation":[{"name":"National Reference Laboratory for Toxoplasmosis, Group for Microbiology and Parasitology, Center of Excellence for Food- and Vector-born Zoonosis, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5086-9017","authenticated-orcid":false,"given":"Vladimir","family":"Dobri\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of Belgrade-Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Srbljanovi\u0107","sequence":"additional","affiliation":[{"name":"National Reference Laboratory for Toxoplasmosis, Group for Microbiology and Parasitology, Center of Excellence for Food- and Vector-born Zoonosis, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9009-1924","authenticated-orcid":false,"given":"Olivera","family":"Lijeski\u0107","sequence":"additional","affiliation":[{"name":"National Reference Laboratory for Toxoplasmosis, Group for Microbiology and Parasitology, Center of Excellence for Food- and Vector-born Zoonosis, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4162-0703","authenticated-orcid":false,"given":"Neda","family":"Bauman","sequence":"additional","affiliation":[{"name":"National Reference Laboratory for Toxoplasmosis, Group for Microbiology and Parasitology, Center of Excellence for Food- and Vector-born Zoonosis, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3514-5328","authenticated-orcid":false,"given":"Vladimir","family":"\u0106irkovi\u0107","sequence":"additional","affiliation":[{"name":"National Reference Laboratory for Toxoplasmosis, Group for Microbiology and Parasitology, Center of Excellence for Food- and Vector-born Zoonosis, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3291-6104","authenticated-orcid":false,"given":"Tijana","family":"\u0160tajner","sequence":"additional","affiliation":[{"name":"National Reference Laboratory for Toxoplasmosis, Group for Microbiology and Parasitology, Center of Excellence for Food- and Vector-born Zoonosis, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,15]]},"reference":[{"key":"ref_1","first-page":"3","article-title":"Acridine: A Versatile Heterocyclic Nucleus","volume":"69","author":"Kumar","year":"2012","journal-title":"Acta Pol. 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