{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:00:20Z","timestamp":1792040420019,"version":"4.4.0"},"reference-count":43,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T00:00:00Z","timestamp":1693872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wroclaw University of Science and Technology\u2019s statue funds","award":["8211104160"],"award-info":[{"award-number":["8211104160"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Among the various substances that interfere with the microtubule formation process, isothiocyanates (ITCs) are the group of compounds for which the binding mode and mechanism of action have not yet been explained. To better understand the structure\u2013activity relationship of tubulin-isothiocyanate interactions, we designed and synthesized a series of sixteen known and novel, structurally diverse ITCs, including amino acid ester-derived isothiocyanates, bis-isothiocyanates, analogs of benzyl isothiocyanate, and phosphorus analogs of sulforaphane. All synthesized compounds and selected natural isothiocyanates (BITC, PEITC, AITC, and SFN) were tested in vitro to evaluate their antiproliferative activity, tubulin polymerization inhibition potential, and influence on cell cycle progression. The antiproliferative activity of most of the newly tested compounds exceeded the action of natural isothiocyanates, with four structures being more potent as tubulin polymerization inhibitors than BITC. As a confirmation of anti-tubulin activity, the correlation between polymerization inhibition and cell cycle arrest in the G2\/M phase was observed for the most active compounds. In light of the biological results indicating significant differences in the impact of structurally diverse isothiocyanate on tubulin polymerization, in silico analysis was conducted to analyze the possible mode of isothiocyanate-tubulin binding and to show how it can influence the polymerization reaction.<\/jats:p>","DOI":"10.3390\/ijms241813674","type":"journal-article","created":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T09:46:20Z","timestamp":1693907180000},"page":"13674","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Isothiocyanates as Tubulin Polymerization Inhibitors\u2014Synthesis and Structure\u2013Activity Relationship Studies"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4064-2409","authenticated-orcid":false,"given":"Renata","family":"Grzywa","sequence":"first","affiliation":[{"name":"Department of Organic and Medicinal Chemistry, Faculty of Chemistry, Wroc\u0142aw University of Science and Technology, Wybrze\u017ce Wyspia\u0144skiego 27, 50-370 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8866-7149","authenticated-orcid":false,"given":"Mateusz","family":"Psurski","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Rudolf Weigl St., 53-114 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gajda","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, 116 Stefan \u017beromski St., 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadeusz","family":"Gajda","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, 116 Stefan \u017beromski St., 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4689-1622","authenticated-orcid":false,"given":"\u0141ukasz","family":"Janczewski","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, 116 Stefan \u017beromski St., 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1039\/B515619J","article-title":"Anticancer Drugs from Nature\u2014Natural Products as a Unique Source of New Microtubule-Stabilizing Agents","volume":"24","author":"Altmann","year":"2007","journal-title":"Nat. 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