{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T02:09:54Z","timestamp":1776305394809,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,5,15]],"date-time":"2019-05-15T00:00:00Z","timestamp":1557878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["DEC-2012\/07\/B\/ST5\/02006"],"award-info":[{"award-number":["DEC-2012\/07\/B\/ST5\/02006"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005888","name":"Medical University of \u0141\u00f3d\u017a","doi-asserted-by":"publisher","award":["No. 503\/1-156-02\/503-11-02."],"award-info":[{"award-number":["No. 503\/1-156-02\/503-11-02."]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In the search for new anticancer agents, a library of variously substituted 3-methylidenechroman-4-ones was synthesized using Horner\u2013Wadsworth\u2013Emmons methodology. Acylation of diethyl methylphosphonate with selected ethyl salicylates furnished 3-diethoxyphosphorylchromen-4-ones which were next used as Michael acceptors in the reaction with various Grignard reagents. The adducts were obtained as the mixtures of trans and cis diastereoisomers along with a small amount of enol forms. Their relative configuration and preferred conformation were established by NMR analysis. The adducts turned up to be effective Horner\u2013Wadsworth\u2013Emmons reagents giving 2-substituted 3-methylidenechroman-4-ones, which were then tested for their possible cytotoxic activity against two leukemia cell lines, HL-60 and NALM-6, and against MCF-7 breast cancer cell line. All new compounds (14a\u2013o) were highly cytotoxic for the leukemic cells and showed a moderate or weak effect on MCF-7 cells. Analog 14d exhibited the highest growth inhibitory activity and was more potent than carboplatin against HL-60 (IC50 = 1.46 \u00b1 0.16 \u00b5M) and NALM-6 (IC50 = 0.50 \u00b1 0.05 \u00b5M) cells. Further tests showed that 14d induced apoptosis in NALM-6 cells, which was mediated mostly through the extrinsic pathway.<\/jats:p>","DOI":"10.3390\/molecules24101868","type":"journal-article","created":{"date-parts":[[2019,5,15]],"date-time":"2019-05-15T11:37:40Z","timestamp":1557920260000},"page":"1868","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synthesis and Cytotoxic Evaluation of 3-Methylidenechroman-4-ones"],"prefix":"10.3390","volume":"24","author":[{"given":"Jacek","family":"K\u0119dzia","sequence":"first","affiliation":[{"name":"Institute of Organic Chemistry, Lodz University of Technology, \u017beromskiego 116, 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Bartosik","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Lodz University of Technology, \u017beromskiego 116, 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Drogosz","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, Medical University of \u0141\u00f3d\u017a, Mazowiecka 6\/8, 92-215 \u0141\u00f3d\u017a, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Janecka","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, Medical University of \u0141\u00f3d\u017a, Mazowiecka 6\/8, 92-215 \u0141\u00f3d\u017a, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urszula","family":"Krajewska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Faculty of Pharmacy, Medical University of \u0141\u00f3d\u017a, Muszy\u0144skiego 1, 90-151 \u0141\u00f3d\u017a, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4898-1405","authenticated-orcid":false,"given":"Tomasz","family":"Janecki","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Lodz University of Technology, \u017beromskiego 116, 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nibbs, A.E., and Scheidt, K.A. 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