{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:38:58Z","timestamp":1786534738000,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005322","name":"Recep Tayyip Erdo\u011fan University","doi-asserted-by":"publisher","award":["02026006012401"],"award-info":[{"award-number":["02026006012401"]}],"id":[{"id":"10.13039\/501100005322","id-type":"DOI","asserted-by":"publisher"}]},{"award":["02026006012401"],"award-info":[{"award-number":["02026006012401"]}],"id":[{"id":"https:\/\/ror.org\/0468j1635","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Benzimidazole and hydrazone scaffolds are widely investigated in anticancer drug discovery because of their structural versatility and capacity to interact with multiple cancer-related targets. This study aimed to synthesize a series of trifluoromethyl-substituted benzimidazole-hydrazone derivatives, evaluate their antiproliferative activity and cancer-cell selectivity, and explore their potential interactions with breast cancer-associated molecular targets. Methods: A series of benzimidazole-hydrazone derivatives were prepared through a four-step synthetic route using both conventional and microwave-assisted procedures. The structures of the synthesized compounds were characterized using spectroscopic and analytical methods. Antiproliferative activity was evaluated in estrogen receptor-positive MCF-7 human breast cancer cells using the MTT assay after 48 h of exposure. Selected active compounds were additionally tested against non-tumorigenic hTERT cells to determine their selectivity indices. In silico analyses were performed against estrogen receptor alpha in antagonist and selective estrogen receptor degrader conformations, bromodomain-containing protein 4, and the mTOR kinase domain. Results: Microwave irradiation substantially reduced reaction times from 12\u201324 h to 4\u20136 min and increased isolated yields by 7\u201324 percentage points compared with conventional conditions. Compounds 4, 7, 9, and 11 reduced MCF-7 cell viability below 50% at 20 \u03bcM. Compound 7 showed the highest antiproliferative activity, with an IC50 value of 7.5 \u00b1 0.8 \u03bcM, and the greatest selectivity toward MCF-7 cells over hTERT cells, with a selectivity index of 12.66. Molecular docking, MD simulation, and MM\/GBSA calculations predicted that compound 7 would effectively bind to the investigated targets, particularly estrogen receptor alpha, as well as the BRD4 and mTOR kinase domains. Conclusions: Compound 7 represents a selective, mid-micromolar benzimidazole-hydrazone lead against MCF-7 breast cancer cells. Its predicted molecular interactions warrant further target-based, mechanistic, pharmacokinetic, and in vivo evaluation.<\/jats:p>","DOI":"10.3390\/ph19081270","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:30:32Z","timestamp":1786465832000},"page":"1270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Trifluoromethyl-Benzimidazole-Hydrazone Derivatives as Promising Selective Anticancer Agents: Synthesis, Cytotoxicity, and Molecular Docking Insights"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1980-1364","authenticated-orcid":false,"given":"Musa","family":"\u00d6zil","sequence":"first","affiliation":[{"name":"Department of Chemistry, Recep Tayyip Erdogan University, Rize 53100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ey\u00fcp","family":"\u00d6nelge","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Recep Tayyip Erdogan University, Rize 53100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9489-9093","authenticated-orcid":false,"given":"Mustafa","family":"Emirik","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Recep Tayyip Erdogan University, Rize 53100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0047-8368","authenticated-orcid":false,"given":"K\u00fcbra","family":"Acikalin Coskun","sequence":"additional","affiliation":[{"name":"Division of Medicinal Biology, Department of Basic Medical Sciences, Istanbul Ayd\u0131n University, Istanbul 34295, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2613-9644","authenticated-orcid":false,"given":"Yusuf","family":"Tutar","sequence":"additional","affiliation":[{"name":"Division of Medical Biochemistry, Department of Basic Medical Sciences, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139376","DOI":"10.1016\/j.molstruc.2024.139376","article-title":"Novel hybrid motifs of 2-(2-pyridinyl)-1H-benzo[d]imidazole-1,2,3-triazole: Synthesis, anticancer assessment, and in silico study","volume":"1318","year":"2024","journal-title":"J. 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