{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T04:47:19Z","timestamp":1786942039578,"version":"build-2736575974"},"reference-count":66,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"MCINN\/AEI\/10.13039\/501100011033","doi-asserted-by":"publisher","award":["PID2021-127471OB-I00"],"award-info":[{"award-number":["PID2021-127471OB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"MCINN\/AEI\/10.13039\/501100011033","doi-asserted-by":"publisher","award":["SA116P20"],"award-info":[{"award-number":["SA116P20"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Consejer\u00eda de Educaci\u00f3n de la Junta de Castilla y Le\u00f3n","award":["PID2021-127471OB-I00"],"award-info":[{"award-number":["PID2021-127471OB-I00"]}]},{"name":"Consejer\u00eda de Educaci\u00f3n de la Junta de Castilla y Le\u00f3n","award":["SA116P20"],"award-info":[{"award-number":["SA116P20"]}]},{"name":"European Union (EU)","award":["PID2021-127471OB-I00"],"award-info":[{"award-number":["PID2021-127471OB-I00"]}]},{"name":"European Union (EU)","award":["SA116P20"],"award-info":[{"award-number":["SA116P20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Antimitotic agents are one of the more successful types of anticancer drugs, but they suffer from toxicity and resistance. The application of approved drugs to new indications (i.e., drug repurposing) is a promising strategy for the development of new drugs. It relies on finding pattern similarities: drug effects to other drugs or conditions, similar toxicities, or structural similarity. Here, we recursively searched a database of approved drugs for structural similarity to several antimitotic agents binding to a specific site of tubulin, with the expectation of finding structures that could fit in it. These searches repeatedly retrieved frentizole, an approved nontoxic anti-inflammatory drug, thus indicating that it might behave as an antimitotic drug devoid of the undesired toxic effects. We also show that the usual repurposing approach to searching for targets of frentizole failed in most cases to find such a relationship. We synthesized frentizole and a series of analogs to assay them as antimitotic agents and found antiproliferative activity against HeLa tumor cells, inhibition of microtubule formation within cells, and arrest at the G2\/M phases of the cell cycle, phenotypes that agree with binding to tubulin as the mechanism of action. The docking studies suggest binding at the colchicine site in different modes. These results support the repurposing of frentizole for cancer treatment, especially for glioblastoma.<\/jats:p>","DOI":"10.3390\/ijms242417474","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T03:16:33Z","timestamp":1702610193000},"page":"17474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Frentizole, a Nontoxic Immunosuppressive Drug, and Its Analogs Display Antitumor Activity via Tubulin Inhibition"],"prefix":"10.3390","volume":"24","author":[{"given":"Sergio","family":"Ramos","sequence":"first","affiliation":[{"name":"Laboratorio de Qu\u00edmica Org\u00e1nica y Farmac\u00e9utica, Departamento de Ciencias Farmac\u00e9uticas, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n de Enfermedades Tropicales de la Universidad de Salamanca (CIETUS), Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Vicente-Bl\u00e1zquez","sequence":"additional","affiliation":[{"name":"Laboratorio de Qu\u00edmica Org\u00e1nica y Farmac\u00e9utica, Departamento de Ciencias Farmac\u00e9uticas, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n de Enfermedades Tropicales de la Universidad de Salamanca (CIETUS), Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"L\u00f3pez-Rubio","sequence":"additional","affiliation":[{"name":"Laboratorio de Qu\u00edmica Org\u00e1nica y Farmac\u00e9utica, Departamento de Ciencias Farmac\u00e9uticas, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n de Enfermedades Tropicales de la Universidad de Salamanca (CIETUS), Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8301-2784","authenticated-orcid":false,"given":"Laura","family":"Gallego-Yerga","sequence":"additional","affiliation":[{"name":"Laboratorio de Qu\u00edmica Org\u00e1nica y Farmac\u00e9utica, Departamento de Ciencias Farmac\u00e9uticas, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n de Enfermedades Tropicales de la Universidad de Salamanca (CIETUS), Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6890-8416","authenticated-orcid":false,"given":"Raquel","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Laboratorio de Qu\u00edmica Org\u00e1nica y Farmac\u00e9utica, Departamento de Ciencias Farmac\u00e9uticas, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n de Enfermedades Tropicales de la Universidad de Salamanca (CIETUS), Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1433-1612","authenticated-orcid":false,"given":"Rafael","family":"Pel\u00e1ez","sequence":"additional","affiliation":[{"name":"Laboratorio de Qu\u00edmica Org\u00e1nica y Farmac\u00e9utica, Departamento de Ciencias Farmac\u00e9uticas, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n de Enfermedades Tropicales de la Universidad de Salamanca (CIETUS), Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37008 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/ijc.33588","article-title":"Cancer statistics for the year 2020: An overview","volume":"149","author":"Ferlay","year":"2021","journal-title":"Int. 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