title: Antifibrotic and anticancer action of 5-ene amino/iminothiazolidinones.
abstract: Here we describe the synthesis and the antifibrotic and anticancer activity determination of amino(imino)thiazolidinone derivatives. An efficient one-pot three-component reaction which involved [2 + 3]-cyclocondensation and Knoevenagel condensation was used for the synthesis of 5-ene-2-amino(imino)-4-thiazolidinones. Following amino-imino tautomerism, the compound structures were confirmed by X-ray analysis. Comparison of SRB assays on fibroblasts and cancer cells revealed that compounds which significantly reduced the viability of fibroblasts did not possess an anticancer effect. A series of thiazolidinone derivatives as interesting candidates for further testing has been identified. Among the tested compounds 2-{3-furan-2-ylmethyl-2-[(2-methyl-3-phenylallylidene)hydrazono]-thiazolidin-4-one-5-yl}-N-(3-trifluoromethylphenyl)-acetamide (5), N-(2-methoxyphenyl)-2-[5-(4-oxothiazolidin-2-ylideneamino)-[1,3,4]thiadiazol-2-ylsulfanyl]-acetamide (12), 3-[3-allyl-4-oxo-2-(thiazol-2-ylimino)thiazolidin-5-ylidene]-1,3-dihydroindol-2-one (33), and 5(Z)-(thiophen-2-ylmethylene)-4-(4-chlorophenylamino)thiazol-2(5H)-one (34) possessed high antifibrotic activity levels, had a similar effect as Pirfenidone, and did not scavenge superoxide radicals. Their antifibrotic potential was confirmed using the xCelligence system.
authors.affiliation: Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, Lviv, 79010, Ukraine.
authors.forename: Danylo
authors.initials: D
authors.lastname: Kaminskyy
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Gertjan J M
authors.initials: GJM
authors.lastname: den Hartog
authors.affiliation: Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, Lviv, 79010, Ukraine.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Wojtyra
authors.affiliation: Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, Lviv, 79010, Ukraine.
authors.forename: Maryan
authors.initials: M
authors.lastname: Lelyukh
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, Karol Marcinkowski Poznan University of Medical Sciences, Grunwaldzka 6, Poznan, 60780, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Gzella
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Aalt
authors.initials: A
authors.lastname: Bast
authors.affiliation: Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, Lviv, 79010, Ukraine. Electronic address: dr_r_lesyk@org.lviv.net.
authors.forename: Roman
authors.initials: R
authors.lastname: Lesyk
mesh_terms: D000586:Amination; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy / Q000378:metabolism; D007097:Imines / Q000737:chemistry / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D013481:Superoxides / Q000378:metabolism; D053778:Thiazolidines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007097:Imines; D053778:Thiazolidines; D013481:Superoxides
keywords: Amino/amino-thiazolidinones; Antifibrotic activity; Antiproliferative effects; One-pot method; Superoxide radicals; Synthesis