{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:40:48Z","timestamp":1785307248696,"version":"3.55.0"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:00:00Z","timestamp":1698883200000},"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><jats:bold>Introduction:<\/jats:bold> FLLL-32, a synthetic analog of curcumin, is a potent inhibitor of STAT3\u2019s constitutive activation in a variety of cancer cells, and its anticancer properties have been demonstrated both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. It is also suggested that it might have other pharmacological activities including activity against different parasites.<\/jats:p><jats:p><jats:bold>Aim:<\/jats:bold> This study therefore investigated the <jats:italic>in vitro<\/jats:italic> antiparasitic activity of FLLL-32 against four pathogenic <jats:italic>Babesia<\/jats:italic> species, <jats:italic>B. bovis<\/jats:italic>, <jats:italic>B. bigemina<\/jats:italic>, <jats:italic>B. divergens<\/jats:italic>, and <jats:italic>B. caballi<\/jats:italic>, and one <jats:italic>Theileria<\/jats:italic> species, <jats:italic>Theileria equi<\/jats:italic>. <jats:italic>In vivo<\/jats:italic> anti-Babesia microti activity of FLLL-32 was also evaluated in mice.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The FLLL-32, in the growth inhibition assay with a concentration range (0.005\u201350\u00a0\u03bcM), was tested for it\u2019s activity against these pathogens. The reverse transcription PCR (RT-PCR) assay was used to evaluate the possible effects of FLLL-32 treatment on the mRNA transcription of the target <jats:italic>B. bovis<\/jats:italic> genes including <jats:italic>S-adenosylhomocysteine hydrolase<\/jats:italic> and <jats:italic>histone deacetylase<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The <jats:italic>in vitro<\/jats:italic> growth of <jats:italic>B. bovis<\/jats:italic>, <jats:italic>B. bigemina<\/jats:italic>, <jats:italic>B. divergens<\/jats:italic>, <jats:italic>B. caballi<\/jats:italic>, and <jats:italic>T. equi<\/jats:italic> was significantly inhibited in a dose-dependent manner (in all cases, <jats:italic>p<\/jats:italic> &amp;lt; 0.05). FLLL-32 exhibits the highest inhibitory effects on <jats:italic>B. bovis<\/jats:italic> growth <jats:italic>in vitro<\/jats:italic>, and it\u2019s IC<jats:sub>50<\/jats:sub> value against this species was 9.57\u00a0\u03bcM. The RT-PCR results showed that FLLL-32 inhibited the transcription of the <jats:italic>B. bovis S-adenosylhomocysteine hydrolase<\/jats:italic> gene. <jats:italic>In vivo<\/jats:italic>, the FLLL-32 showed significant inhibition (<jats:italic>p<\/jats:italic> &amp;lt; 0.05) of <jats:italic>B. microti<\/jats:italic> parasitemia in infected mice with results comparable to that of diminazene aceturate. Parasitemia level in <jats:italic>B. microti<\/jats:italic>-infected mice treated with FLLL-32 from day 12 post infection (pi) was reduced to reach zero level at day 16 pi when compared to the infected non-treated mice.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The present study demonstrated the antibabesial properties of FLLL-32 and suggested it\u2019s usage in the treatment of babesiosis especially when utilized in combination therapy with other antibabesial drugs.<\/jats:p>","DOI":"10.3389\/fphar.2023.1278451","type":"journal-article","created":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T09:27:10Z","timestamp":1698917230000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Antiparasitic activity of FLLL-32 against four Babesia species, B. bovis, B. bigemina, B. divergens and B. caballi, and one Theileria species, Theileria equi in vitro, and Babesia microti in mice"],"prefix":"10.3389","volume":"14","author":[{"given":"Shimaa Abd El-Salam","family":"El-Sayed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El-Sayed","family":"El-Alfy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanadi B.","family":"Baghdadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Z.","family":"Sayed-Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad S.","family":"Alqahtani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawazish","family":"Alam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarfaraz","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. 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