{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T12:22:02Z","timestamp":1791634922740,"version":"4.3.4"},"reference-count":127,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Despite notable progress in drug discovery, cancer treatment remains hindered by limited therapeutic efficacy, poor target specificity, adverse effects, and the development of drug resistance. Molecular hybridization, which integrates two or more bioactive entities into a single molecule, has shown considerable potential to overcome these limitations. Since both azoles and flavonoids have demonstrated anticancer potential, extensive studies have been undertaken to combine the two entities and enhance the bioactivity of the resulting hybrids. In this context, numerous azole\u2013flavonoid hybrids have been synthesized and investigated for their anticancer potential. This review provides an overview of the azole\u2013flavonoid hybrids that are promising candidates for novel anticancer drug development, highlighting their superior antitumor potency compared to reference drugs, multitarget activity, tumor-selective cytotoxicity, efficacy against drug-resistant tumor cells, and structure\u2013activity relationships. The review covers 250 hybrids, primarily triazole\u2013chalcone hybrids but also triazole\u2013flavone, flavanone, flavonol, and isoflavone hybrids, as well as other azole\u2013flavonoid hybrids (imidazole\u2013, pyrazole\u2013, isoxazole\u2013, and thiazole\u2013flavonoid hybrids).<\/jats:p>","DOI":"10.3390\/ph19020338","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T13:08:23Z","timestamp":1771592903000},"page":"338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Azole\u2013Flavonoid Hybrids as Emerging Anticancer Agents: A Bioactivity-Focused Review"],"prefix":"10.3390","volume":"19","author":[{"given":"Mihaela","family":"Lipovanu","sequence":"first","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 16, Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Miron","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 16, Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0949-7538","authenticated-orcid":false,"given":"Nina","family":"Filip","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 16, Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4168-9938","authenticated-orcid":false,"given":"Cristina Elena","family":"Horhogea","sequence":"additional","affiliation":[{"name":"Ion Ionescu de la Brad Iasi University of Life Sciences, 3, Mihail Sadoveanu Alley, 700489 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Clara","family":"Aprotosoaie","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 16, Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.2174\/1871520616666161221112042","article-title":"Role of Azoles in Cancer Prevention and Treatment: Present and Future Perspectives","volume":"18","author":"Ahmad","year":"2018","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Szumilak, M., Wiktorowska-Owczarek, A., and Stanczak, A. (2021). Hybrid Drugs\u2014A Strategy for Overcoming Anticancer Drug Resistance?. Molecules, 26.","DOI":"10.3390\/molecules26092601"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Singh, A.K., Kumar, A., Singh, H., Sonawane, P., Paliwal, H., Thareja, S., Pathak, P., Grishina, M., Jaremko, M., and Emwas, A.H. (2022). 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