{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:38Z","timestamp":1787027858949,"version":"build-2736575974"},"reference-count":73,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Advanced-stage hepatocellular carcinoma is characterized by a very poor prognosis; thus, highly effective medication is still needed. Often overexpressed heat shock protein 90 is a promising target due to its pivotal role in carcinogenesis. Methods: Antiproliferative effects of 246TMP-3SF5 on HepG2 and HuH-7 cells were assessed by crystal violet staining. Apoptosis was evaluated via subG1 peak, caspase-3 activity and PARP cleavage, and ferroptosis via ROS, glutathione and malondialdehyde levels. Migration was assessed by scratch assay, and in ovo models were used to study angiogenesis and drug effects on microtumors. CAM vascular networks were quantified by semi-automatic segmentation, morphometric and box-counting fractal analysis. Molecular docking and molecular dynamics simulation of heat shock protein 90 were carried out using Autodock Vina and Gromacs respectively. Results: Profound dose- and time-dependent antiproliferative effects of 246TMP-3SF5 against HCC cell lines were observed, revealing low micromolecular IC50 values and selectivity for carcinoma cells with selectivity indices &gt; 1. A significant increase in the sub-G1 peak, key effector caspase-3 activity, as well as cleavage of PARP strongly suggested apoptosis playing a crucial role in the antiproliferative effects. Additionally, HuH-7 cells revealed an elevation of reactive oxygen species and both cell lines showed significant glutathione depletion concomitant with an increase in malondialdehyde concentration upon treatment. The observed effect could be partially reversed by applying ferrostatin-1, suggesting ferroptosis as an additional relevant mode of action. Changes in the cell cycle as well as impaired tumor cell migration were observed. Upon treatment, angiogenesis was impaired and mass of microtumors was significantly reduced. Quantitative CAM analysis showed that vascularized area fraction increased in controls but decreased under both 17-AAG and 246TMP-3SF5. Likewise global mean vessel width decreased relative to controls, while box-counting dimension was reduced under 246TMP-3SF5. Molecular docking and molecular dynamics simulation analysis predicts 246TMP-3SF5 to be binding in catalytic site of heat shock protein 90. Conclusions: 246TMP-3SF5 is a promising novel inhibitor meriting further research as a potential treatment against hepatocellular carcinoma.<\/jats:p>","DOI":"10.3390\/cancers18162640","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T10:04:36Z","timestamp":1786961076000},"page":"2640","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of the New Pentafluorosulfanyl-Substituted Chalcone 246TMP-3SF5 as a Potential New Treatment Option Against Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"18","author":[{"given":"Alessandra","family":"Viperino","sequence":"first","affiliation":[{"name":"Institute of Physiology, Charit\u00e9\u2014University Medical Center Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0557-3927","authenticated-orcid":false,"given":"Linda","family":"Hammerich","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Charit\u00e9\u2014University Medical Center Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7305-346X","authenticated-orcid":false,"given":"Bernhard","family":"Biersack","sequence":"additional","affiliation":[{"name":"Organic Chemistry Laboratory, University Bayreuth, Universit\u00e4tsstrasse 30, 95440 Bayreuth, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supriya","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Macrogene AI, Vadodara 390009, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7693-9098","authenticated-orcid":false,"given":"Ion","family":"Andronache","sequence":"additional","affiliation":[{"name":"Advanced Digital Archaeological-Historical Network (ADAHN), Alma Mater Europaea (AMEU), Slovenska Ulica 17, 2000 Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1705-7571","authenticated-orcid":false,"given":"Isabel","family":"Groth","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Charit\u00e9\u2014University Medical Center Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"Fakult\u00e4t Medizin, MSB Medical School Berlin, <sans-serif>R\u00fcdesheimer Stra\u00dfe 50,<\/sans-serif> 14197 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Edel","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Charit\u00e9\u2014University Medical Center Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0785-9451","authenticated-orcid":false,"given":"Michael","family":"Hoepfner","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Charit\u00e9\u2014University Medical Center Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7916-3344","authenticated-orcid":false,"given":"Bianca","family":"Nitzsche","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Charit\u00e9\u2014University Medical Center Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/S0140-6736(22)01200-4","article-title":"Hepatocellular Carcinoma","volume":"400","author":"Vogel","year":"2022","journal-title":"Lancet"},{"key":"ref_2","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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