{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:37:25Z","timestamp":1790440645965,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T00:00:00Z","timestamp":1615334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Malaria remains one of the major health concerns due to the resistance of <jats:italic>Plasmodium<\/jats:italic> species toward the existing drugs warranting an urgent need for new antimalarials. Thymol derivatives were known to exhibit enhanced antimicrobial activities; however, no reports were found against <jats:italic>Plasmodium<\/jats:italic> spp. In the present study, the antiplasmodial activity of thymol derivatives was evaluated against chloroquine-sensitive (NF-54) and -resistant (K1) strains of <jats:italic>Plasmodium falciparum<\/jats:italic>. Among the thymol derivatives tested, 4-chlorothymol showed potential activity against sensitive and resistant strains of <jats:italic>P. falciparum<\/jats:italic>. 4-Chlorothymol was found to increase the reactive oxygen species and reactive nitrogen species level. Furthermore, 4-chlorothymol could perturb the redox balance by modulating the enzyme activity of GST and GR. 4-Chlorothymol also showed synergy with chloroquine against chloroquine-resistant <jats:italic>P. falciparum<\/jats:italic>. 4-Chlorothymol was found to significantly suppress the parasitemia and increase the mean survival time in <jats:italic>in vivo<\/jats:italic> assays. Interestingly, in <jats:italic>in vivo<\/jats:italic> assay, 4-chlorothymol in combination with chloroquine showed higher chemosuppression as well as enhanced mean survival time at a much lower concentration as compared to individual doses of chloroquine and 4-chlorothymol. These observations clearly indicate the potential use of 4-chlorothymol as an antimalarial agent, which may also be effective in combination with the existing antiplasmodial drugs against chloroquine-resistant <jats:italic>P. falciparum<\/jats:italic> infection. <jats:italic>In vitro<\/jats:italic> cytotoxicity\/hemolytic assay evidently suggests that 4-chlorothymol is safe for further exploration of its therapeutic properties.<\/jats:p>","DOI":"10.3389\/fphar.2021.628970","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T09:01:47Z","timestamp":1615366907000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["4-Chlorothymol Exerts Antiplasmodial Activity Impeding Redox Defense System in Plasmodium falciparum"],"prefix":"10.3389","volume":"12","author":[{"given":"Saurabh","family":"Kumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja Rani","family":"Mina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anirban","family":"Pal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ateeque","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeep","family":"Tandon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahendra P.","family":"Darokar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/0035-9203(90)90129-3","article-title":"In vitro activity of artemisinin, its derivatives, and pyronaridine against different strains of Plasmodium falciparum","volume":"84","author":"Alin","year":"1990","journal-title":"Trans. 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