{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T01:56:24Z","timestamp":1777514184861,"version":"3.51.4"},"reference-count":95,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,3,31]],"date-time":"2019-03-31T00:00:00Z","timestamp":1553990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy Cluj-Napoca","award":["internal research grant No. 4944\/7\/08.03.2016 (Cristina Nastas\u0103)"],"award-info":[{"award-number":["internal research grant No. 4944\/7\/08.03.2016 (Cristina Nastas\u0103)"]}]},{"name":"The Executive Agency for Higher Education Research Development and Innovation Funding - UEFISCDI, Romania","award":["Contract 210\/2014 - Project PN-II-PT-PCCA-2013-4-2075 (Radu Tamaian)"],"award-info":[{"award-number":["Contract 210\/2014 - Project PN-II-PT-PCCA-2013-4-2075 (Radu Tamaian)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and objectives: Cancer represents the miscommunication between and within the body cells. The mutations of the oncogenes encoding the MAPK pathways play an important role in the development of tumoral diseases. The mutations of KRAS and BRAF oncogenes are involved in colorectal cancer and melanoma, while the NRAS mutations are associated with melanoma. Thiazolidine-2,4-dione is a versatile scaffold in medicinal chemistry and a useful tool in the development of new antitumoral compounds. The aim of our study was to predict the pharmacokinetic\/pharmacodynamic properties, the drug-likeness and lead-likeness of two series of synthetic 5-arylidene(chromenyl-methylene)-thiazolidinediones, the molecular docking on the oncoproteins K-Ras, N-Ras and B-Raf, and to investigate the cytotoxicity of the compounds, in order to select the best structural profile for potential anticancer agents. Materials and Methods: In our paper we studied the cytotoxicity of two series of thiazolidine-2,4-dione derivatives, their ADME-Tox properties and the molecular docking on a mutant protein of K-Ras, two isoforms of N-Ras and an isoform of B-Raf with 16 mutations. Results: The heterocyclic compounds strongly interact with K-Ras and N-Ras right after their posttranslational processing and\/or compete with GDP for the nucleotide-binding site of the two GTPases. They are less active against the GDP-bound states of the two targets. All derivatives have a similar binding pattern in the active site of B-Raf. Conclusions: The data obtained encourage the further investigation of the 5-arylidene(chromenyl-methylene)-thiazolidinediones as potential new agents against the oncoproteins K-Ras, N-Ras and B-Raf.<\/jats:p>","DOI":"10.3390\/medicina55040085","type":"journal-article","created":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T03:21:26Z","timestamp":1554175286000},"page":"85","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["5-Arylidene(chromenyl-methylene)-thiazolidinediones: Potential New Agents against Mutant Oncoproteins K-Ras, N-Ras and B-Raf in Colorectal Cancer and Melanoma"],"prefix":"10.3390","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5803-6108","authenticated-orcid":false,"given":"Cristina","family":"Nastas\u0103","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical chemistry, Faculty of Pharmacy, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 41 Victor Babe\u0219 Street, RO-400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6380-1460","authenticated-orcid":false,"given":"Radu","family":"Tamaian","sequence":"additional","affiliation":[{"name":"National Research and Development Institute for Cryogenics and Isotopic Technologies, ICSI Analytics, 4th Uzinei Street, RO-240050 R\u00e2mnicu V\u00e2lcea, Romania"},{"name":"SC Biotech Corp SRL, 4th Uzinei Street, RO-240050 R\u00e2mnicu V\u00e2lcea, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ovidiu","family":"Oniga","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical chemistry, Faculty of Pharmacy, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 41 Victor Babe\u0219 Street, RO-400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1333-5649","authenticated-orcid":false,"given":"Br\u00eendu\u0219a","family":"Tiperciuc","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical chemistry, Faculty of Pharmacy, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 41 Victor Babe\u0219 Street, RO-400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.1038\/sj.onc.1210421","article-title":"MAP kinase signalling pathways in cancer","volume":"26","author":"Dhillon","year":"2007","journal-title":"Oncogene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1177\/1947601911411084","article-title":"Ras in cancer and developmental diseases","volume":"2","author":"Santos","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_3","first-page":"38892","article-title":"RAS-MAPK pathway epigenetic activation in cancer: miRNAs in action","volume":"7","author":"Garinet","year":"2015","journal-title":"Oncotarget"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1158\/1078-0432.CCR-09-2446","article-title":"Prevalence and Heterogeneity of KRAS, BRAF, and PIK3CA Mutations in Primary Colorectal Adenocarcinomas and Their Corresponding Metastases","volume":"16","author":"Baldus","year":"2010","journal-title":"Clin. 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