{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T19:14:33Z","timestamp":1773861273604,"version":"3.50.1"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Toxoplasmosis is one of the most prevalent and neglected zoonotic global diseases caused by <jats:italic>Toxoplasma gondii<\/jats:italic>. The current pharmacological treatments show clinical limitations, and therefore, the search for new drugs is an urgent need in order to eradicate this infection. Due to their intrinsic biological activities, \u03b2-carboline (\u03b2C) alkaloids might represent a good alternative that deserves further investigations. In this context, the <jats:italic>in vitro<\/jats:italic> anti-<jats:italic>T. gondii<\/jats:italic> activity of three \u03b2Cs, harmine (<jats:bold>1<\/jats:bold>), 2-methyl-harminium (<jats:bold>2<\/jats:bold>), and 9-methyl-harmine (<jats:bold>3<\/jats:bold>), was evaluated herein. Briefly, the three alkaloids exerted direct effects on the parasite invasion and\/or replication capability. Replication rates of intracellular treated tachyzoites were also affected in a dose-dependent manner, at noncytotoxic concentrations for host cells. Additionally, cell cycle analysis revealed that both methyl-derivatives <jats:bold>2<\/jats:bold> and <jats:bold>3<\/jats:bold> induce parasite arrest in S\/M phases. Compound <jats:bold>3<\/jats:bold> showed the highest irreversible parasite growth inhibition, with a half maximal inhibitory concentration (IC50) value of 1.8 \u00b1 0.2 \u03bcM and a selectivity index (SI) of 17.2 at 4 days post infection. Due to high replication rates, tachyzoites are frequently subjected to DNA double-strand breaks (DSBs). This highly toxic lesion triggers a series of DNA damage response reactions, starting with a kinase cascade that phosphorylates a large number of substrates, including the histone H2A.X to lead the early DSB marker \u03b3H2A.X. Western blot studies showed that basal expression of \u03b3H2A.X was reduced in the presence of <jats:bold>3<\/jats:bold>. Interestingly, the typical increase in \u03b3H2A.X levels produced by camptothecin (CPT), a drug that generates DSB, was not observed when CPT was co-administered with <jats:bold>3<\/jats:bold>. These findings suggest that <jats:bold>3<\/jats:bold> might disrupt <jats:italic>Toxoplasma<\/jats:italic> DNA damage response.<\/jats:p>","DOI":"10.3389\/fmicb.2021.716534","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T08:39:22Z","timestamp":1628152762000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["In vitro Effect of Harmine Alkaloid and Its N-Methyl Derivatives Against Toxoplasma gondii"],"prefix":"10.3389","volume":"12","author":[{"given":"Maria L.","family":"Alomar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan G.","family":"Ya\u00f1uk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio O.","family":"Angel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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