{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Rehulka J"],"funding":["National Institute for Cancer Research","CZ-OPENSCREEN","EATRIS-CZ","Ministry of Education, Youth and Sports of the Czech Republic through the e-INFRA CZ","EXCELES","UCT Prague"],"pagination":["2367139"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC467089"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["39(1)"],"pubmed_abstract":["Estradiol dimers (EDs) possess significant anticancer activity by targeting tubulin dynamics. In this study, we synthesised 12 EDs variants via copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction, focusing on structural modifications within the aromatic bridge connecting two estradiol moieties. <i>In vitro</i> testing of these EDs revealed a marked improvement in selectivity towards cancerous cells, particularly for ED1-8. The most active compounds, ED3 (IC<sub>50</sub> = 0.38 μM in CCRF-CEM) and ED5 (IC<sub>50</sub> = 0.71 μM in CCRF-CEM) demonstrated cytotoxic effects superior to 2-methoxyestradiol (IC<sub>50</sub> = 1.61 μM in CCRF-CEM) and exhibited anti-angiogenic properties in an endothelial cell tube-formation model. Cell-based experiments and <i>in vitro</i> assays revealed that EDs interfere with mitotic spindle assembly. Additionally, we proposed an <i>in silico</i> model illustrating the probable binding modes of ED3 and ED5, suggesting that dimers with a simple linker and a single substituent on the aromatic central ring possess enhanced characteristics compared to more complex dimers."],"journal":["Journal of enzyme inhibition and medicinal chemistry"],"pubmed_title":["Click estradiol dimers with novel aromatic bridging units: synthesis and anticancer evaluation."],"pmcid":["PMC467089"],"funding_grant_id":["A1_FPBT_2023_003","90254","LX22NPO5102","LM2023052","LM2023053","IGA_LF_2024_038"],"pubmed_authors":["Ivanova A","Gurska S","Polishchuk P","Rehulka J","Drasar PB","Draber P","Dzubak P","Jecmenova K","Hajduch M","Jurasek M","Mokshyna O"],"additional_accession":[]},"is_claimable":false,"name":"Click estradiol dimers with novel aromatic bridging units: synthesis and anticancer evaluation.","description":"Estradiol dimers (EDs) possess significant anticancer activity by targeting tubulin dynamics. In this study, we synthesised 12 EDs variants via copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction, focusing on structural modifications within the aromatic bridge connecting two estradiol moieties. <i>In vitro</i> testing of these EDs revealed a marked improvement in selectivity towards cancerous cells, particularly for ED1-8. The most active compounds, ED3 (IC<sub>50</sub> = 0.38 μM in CCRF-CEM) and ED5 (IC<sub>50</sub> = 0.71 μM in CCRF-CEM) demonstrated cytotoxic effects superior to 2-methoxyestradiol (IC<sub>50</sub> = 1.61 μM in CCRF-CEM) and exhibited anti-angiogenic properties in an endothelial cell tube-formation model. Cell-based experiments and <i>in vitro</i> assays revealed that EDs interfere with mitotic spindle assembly. Additionally, we proposed an <i>in silico</i> model illustrating the probable binding modes of ED3 and ED5, suggesting that dimers with a simple linker and a single substituent on the aromatic central ring possess enhanced characteristics compared to more complex dimers.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2026-04-29T12:12:19.215Z","creation":"2025-04-06T17:10:50.957Z"},"accession":"S-EPMC467089","cross_references":{"pubmed":["38904149"],"doi":["10.1080/14756366.2024.2367139"]}}