{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T01:02:20Z","timestamp":1767920540141,"version":"3.49.0"},"reference-count":25,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T00:00:00Z","timestamp":1518480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: Heat shock protein 90 (HSP90) is a well-known target for cancer therapy. In a previous work, some of us have reported a series of 3-aryl-naphtho[2,3-d]isoxazole-4,9-diones as inhibitors of HSP90. Methods: In the present work, various compounds with new chromenopyridinone and thiochromenopyridinone scaffolds were synthesized as potential HSP90 inhibitors. Their binding affinity to HSP90 was studied in vitro. Selected compounds (5 and 8) were further studied in various tumor cell lines regarding their potential to cause cell growth inhibition, alter the cell cycle profile, inhibit proliferation, and induce apoptosis. Their effect on HSP90 client protein levels was also confirmed in two cell lines. Finally, the antitumor activity of compound 8 was studied in A431 squamous cell carcinoma xenografts in nude mice. Results: Our results indicated that treatment with compounds 5 and 8 decreased the proliferation of tumor cell lines and compound 8 induced apoptosis. In addition, these two compounds were able to downregulate selected proteins known as \u201cclients\u201d of HSP90. Finally, treatment of xenografted mice with compound 5 resulted in a considerable dose-dependent inhibition of tumor growth. Conclusions: Our results show that two new compounds with a chromenopyridinone and thiochromenopyridinone scaffold are promising putative HSP90 inhibitors causing tumor cell growth inhibition.<\/jats:p>","DOI":"10.3390\/molecules23020407","type":"journal-article","created":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T14:23:48Z","timestamp":1518531828000},"page":"407","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Synthesis and Evaluation of the Tumor Cell Growth Inhibitory Potential of New Putative HSP90 Inhibitors"],"prefix":"10.3390","volume":"23","author":[{"given":"Ana","family":"Bizarro","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Faculty of Pharmacy of the University of Porto (FFUP), Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Department of Biology, School of Sciences, University of Minho, 4710-057 Braga, Portugal"}]},{"given":"Diana","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Pharmacy of the University of Porto (FFUP), Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade da Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Cancer Drug Resistance Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"}]},{"given":"Raquel","family":"Lima","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade da Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Cancer Drug Resistance Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), Alameda Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Loana","family":"Musso","sequence":"additional","affiliation":[{"name":"Department of Food, Environmental and Nutritional Sciences Division of Chemistry and Molecular Biology, Universit\u00e0 degli Studi di Milano, via Celoria 2, 20133 Milano, Italy"}]},{"given":"Raffaella","family":"Cincinelli","sequence":"additional","affiliation":[{"name":"Department of Food, Environmental and Nutritional Sciences Division of Chemistry and Molecular Biology, Universit\u00e0 degli Studi di Milano, via Celoria 2, 20133 Milano, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7882-9095","authenticated-orcid":false,"given":"Vantina","family":"Zuco","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology and Molecular Medicine, Fondazione, IRCCS\u2014Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milano, Italy"}]},{"given":"Michelandrea","family":"De Cesare","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology and Molecular Medicine, Fondazione, IRCCS\u2014Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milano, Italy"}]},{"given":"Sabrina","family":"Dallavalle","sequence":"additional","affiliation":[{"name":"Department of Food, Environmental and Nutritional Sciences Division of Chemistry and Molecular Biology, Universit\u00e0 degli Studi di Milano, via Celoria 2, 20133 Milano, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7801-4643","authenticated-orcid":false,"given":"M.","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Pharmacy of the University of Porto (FFUP), Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade da Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Cancer Drug Resistance Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2018,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s12192-014-0561-0","article-title":"Small heat shock proteins: Big folding machines","volume":"20","author":"Morrow","year":"2015","journal-title":"Cell Stress Chaperones"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1755-1536-5-7","article-title":"Heat shock protein 27 (HSP27): Biomarker of disease and therapeutic target","volume":"5","author":"Vidyasagar","year":"2012","journal-title":"Fibrogenesis Tissue Repair"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.canlet.2015.02.026","article-title":"The role of heat shock proteins in 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