{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:21:30Z","timestamp":1788448890084,"version":"build-2803163510"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004561","name":"Ministry of Education and Science of the Republic of Kazakhstan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004561","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Chem."],"abstract":"<jats:p>\n                    The persistence of resistance, recurrence, and limited selectivity in cancer therapy necessitates the development of structurally advanced antitumor agents capable of modulating multiple intracellular pathways. This review provides a systematic analysis of nitrogen- and oxygen-containing heterocycles as key platforms in anticancer drug design, with an emphasis on integrated molecular architectures combining multiple pharmacophoric fragments. A central and unifying principle emerging from the analyzed studies is the decisive role of hydrazide\u2013hydrazone functionalization as a pharmacophoric enhancer, which should be considered not merely as a substituent but as a core structural element governing conformational flexibility, electronic distribution, and target-binding efficiency. Its incorporation consistently correlates with enhanced antiproliferative activity, apoptosis induction, and improved selectivity across diverse tumor models. Within this framework, the most efficient representatives highlight the practical significance of this design strategy: compound 17 demonstrates exceptional activity with GI\n                    <jats:sub>50<\/jats:sub>\n                    values of 0.01\u20130.1\u00a0\u03bcM among N-heterocyclic systems, while compound 40 emerges as a leading O-heterocyclic analogue, exhibiting IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 0.45\u00a0\u03bcg\/mL against MCF-7 cells. Collectively, these findings support the strategic prioritization of hydrazide-centered heterocyclic scaffolds as a foundation for the rational development of next-generation anticancer therapeutics.\n                  <\/jats:p>","DOI":"10.3389\/fchem.2026.1861312","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:53:12Z","timestamp":1788447192000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Antitumor and proliferative modulation by N- and O-heterocycles: a comprehensive review of cell growth regulation"],"prefix":"10.3389","volume":"14","author":[{"given":"Nurzhan","family":"Chinibayeva","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Natural Sciences and Geography, Abai Kazakh National Pedagogical University","place":["Almaty City, Kazakhstan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zulfiya","family":"Unerbaeva","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Natural Sciences and Geography, Abai Kazakh National Pedagogical University","place":["Almaty City, Kazakhstan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniil","family":"Shepilov","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Farabi University","place":["Almaty City, Kazakhstan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulzat","family":"Berganayeva","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Farabi University","place":["Almaty City, Kazakhstan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichang","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University","place":["Shihezi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Pu","sequence":"additional","affiliation":[{"name":"Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University","place":["Shihezi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akmaral","family":"Nurmahanova","sequence":"additional","affiliation":[{"name":"Faculty of Biology and Biotechnology, Farabi University","place":["Almaty City, Kazakhstan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulbanu","family":"Zhaksylykova","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Farabi University","place":["Almaty City, Kazakhstan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandugash","family":"Sydykbayeva","sequence":"additional","affiliation":[{"name":"Faculty of Natural and Technical Sciences, Zhetysu University Named After Ilyas Zhansugurov","place":["Taldykorgan, Kazakhstan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moldyr","family":"Dyusebaeva","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Farabi University","place":["Almaty City, Kazakhstan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"23495","DOI":"10.1039\/d4ra03963g","article-title":"Synthesis, characterization and biological research of novel 2-(quinoline-4-carbonyl)hydrazide-acrylamide hybrids as potential anticancer agents","volume":"14","author":"Abd El-Lateef","year":"2024","journal-title":"RSC Adv."},{"key":"B2","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1515\/tjb-2017-0167","article-title":"Synthesis and evaluation of new benzimidazole derivatives with hydrazone moiety as anticancer agents","volume":"43","author":"Acar \u00c7evik","year":"2018","journal-title":"Turkish J. 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