{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:43:03Z","timestamp":1791646983525,"version":"4.3.4"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018786","name":"Al-Zaytoonah University of Jordan","doi-asserted-by":"publisher","award":["30\/06\/2024-2025"],"award-info":[{"award-number":["30\/06\/2024-2025"]}],"id":[{"id":"10.13039\/501100018786","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018786","name":"Al-Zaytoonah University of Jordan","doi-asserted-by":"publisher","award":["27\/06\/2024-2025"],"award-info":[{"award-number":["27\/06\/2024-2025"]}],"id":[{"id":"10.13039\/501100018786","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004242","name":"Princess Nourah Bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2025R418"],"award-info":[{"award-number":["PNURSP2025R418"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec013\">\n<jats:title>Objectives<\/jats:title>\n<jats:p>Fluoroquinolones, such as levofloxacin (LVX), are extended-spectrum drugs used for the treatment of bacterial infections. Several fluoroquinolone derivatives have shown promising antibacterial and anticancer activities. Our group has earlier synthesized and investigated thionated LVX analogs, compounds <jats:bold>2<\/jats:bold> and <jats:bold>3<\/jats:bold>, on A549 (non-small cell lung cancer) cell line and showed promising anticancer activity. The mechanism of cytotoxicity may be, in part, via aldehyde dehydrogenase enzyme inhibition and antioxidation. In this study, compounds <jats:bold>2<\/jats:bold> and <jats:bold>3<\/jats:bold> were evaluated on prostate (PC-3), breast (MCF7), colorectal (Caco-2), and small cell lung cancer (H69 and H69AR) cell lines.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec014\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The anticancer activity was measured using resazurin colorimetric method. Combination treatments with doxorubicin (DOX) were also employed and combination index (CI) value were calculated.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec015\">\n<jats:title>Results<\/jats:title>\n<jats:p>Compound <jats:bold>3<\/jats:bold> possessed higher anticancer activity compared to compound <jats:bold>2<\/jats:bold> on the tested cancer cell lines. Compound <jats:bold>3<\/jats:bold> had the highest activity on PC-3 cells with IC<jats:sub>50<\/jats:sub> value of 3.58 \u00b5M. DOX was also tested for comparison and had IC<jats:sub>50<\/jats:sub> value of less than 0.5 \u00b5M in all tested cell lines except for H69AR (DOX-resistant form of H69), which was 4.62 \u00b5M. Combination treatment with DOX resulted in significant reduction of cell viability in PC-3, H69, and H69AR cells, with those on H69 and H69AR cells resulted in additive (CI\u2009=\u20091.0) and synergistic effects (CI\u2009=\u20090.6), respectively.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec016\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Compound <jats:bold>3<\/jats:bold>, a thionated LVX derivative, showed a promising anticancer activity, prompting its potential repurposing for cancer treatment as well as combination treatment with DOX on DOX-resistant cancer cells.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0324930","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T17:44:11Z","timestamp":1749491051000},"page":"e0324930","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Thionated levofloxacin derivative: Potential repurposing for cancer treatment and synergism with doxorubicin on doxorubicin-resistant lung cancer cells"],"prefix":"10.1371","volume":"20","author":[{"given":"Hamza","family":"Abumansour","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0856-5618","authenticated-orcid":true,"given":"Osama H.","family":"Abusara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Abu-Sini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiam","family":"Khalil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali I. 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