Design, synthesis, and anticancer activity of novel 4-thiazolidinone-phenylaminopyrimidine hybrids

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dc.authoridTure, Asli/0000-0003-3422-7425
dc.authoridErgul, Mustafa/0000-0003-4303-2996
dc.authoridAltun, Ahmet/0000-0003-2056-8683
dc.contributor.authorTure, Asli
dc.contributor.authorErgul, Mustafa
dc.contributor.authorErgul, Merve
dc.contributor.authorAltun, Ahmet
dc.contributor.authorKucukguzel, Ilkay
dc.date.accessioned2024-10-26T18:07:33Z
dc.date.available2024-10-26T18:07:33Z
dc.date.issued2021
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstract4-Thiazolidinones and phenylaminopyrimidines are known as anticancer agents. Imatinib is the pioneer phenylaminopyrimidine derivative kinase inhibitor, which is used for the treatment of chronic myeloid leukemia. With a hybrid approach, a novel series of 5-benzylidene-2-arylimino-4-thiazolidinone derivatives containing phenylaminopyrimidine core were designed, synthesized, and tested for their anticancer activity on K562 (chronic myeloid leukemia), PC3 (prostat cancer), and SHSY-5Y (neuroblastoma) cells. Since superior anticancer activity was observed on K562 cells, further biological studies of selected compounds (8, 15, and 34) were performed on K562 cells. For the synthesis of designed compounds, thiourea compounds were converted to 2-imino-1,3-thiazolidin-4-ones with alpha-chloroacetic acid in the presence of sodium acetate. 5-Benzylidene-2-imino-1,3-thiazolidin-4-one derivatives were obtained by Knoevenagel condensation of 2-imino-1,3-thiazolidin-4-ones with related aldehydes. Compounds 8, 15, and 34 were evaluated for cell viability, apoptosis studies, cell cycle experiments, and DNA damage assays. IC50 values of compounds 8, 15, and 34 were found as 5.26 +/- 1.03, 3.52 +/- 0.91, and 8.16 +/- 1.27 mu M, respectively, in K562 cells. Preferably, these compounds showed less toxicity towards L929 cells compared to imatinib. Furthermore, compounds 8 and 15 significantly induced early and late apoptosis in a time-dependent manner. Compounds 15 and 34 induced cell cycle arrest at G0/G1 phase and compound 8 caused cell cycle arrest at G2/M phase. Based on DNA damage assay, compounds 8 and 15 were found to be more genotoxic than imatinib towards K562 cells. To put more molecular insight, possible Abl inhibition mechanisms of most active compounds were predicted by molecular docking studies. In conclusion, a novel series of 5-benzylidene-2-arylimino-4-thiazolidinone derivatives and their promising anticancer activities were reported herein. [GRAPHICS] .
dc.description.sponsorshipResearch Fund of Marmara University [SAG-C-DRP-111115-0502]; Research Fund of Sivas Cumhuriyet University (CuBAP) [ECZ-046]; Scientific and Technological Research Council of Turkey (TuBTAK) under the National Scholarship Programme
dc.description.sponsorshipThis work was supported by the Research Fund of Marmara University with the project number: SAG-C-DRP-111115-0502. This work was also financially supported by the Research Fund of Sivas Cumhuriyet University (CuBAP) with the project number: ECZ-046. During this research, Asl Ture was granted by the Scientific and Technological Research Council of Turkey (TuBTAK) under the National Scholarship Programme for PhD Students in Natural Sciences, Medical Sciences, Social Sciences and Humanities and Engineering and Technological Sciences. The authors are grateful to Prof. Dr. Habil. Wolfgang Sippl for giving the opportunity to use Schrodinger software. Authors also would like to thank DEVA Pharmaceuticals for donation of imatinib mesylate and 4-methyl-N3-[4-(pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine specimens for our research.
dc.identifier.doi10.1007/s11030-020-10087-1
dc.identifier.endpage1050
dc.identifier.issn1381-1991
dc.identifier.issn1573-501X
dc.identifier.issue2
dc.identifier.pmid32328961
dc.identifier.scopus2-s2.0-85084146195
dc.identifier.scopusqualityQ2
dc.identifier.startpage1025
dc.identifier.urihttps://doi.org/10.1007/s11030-020-10087-1
dc.identifier.urihttps://hdl.handle.net/20.500.12418/29568
dc.identifier.volume25
dc.identifier.wosWOS:000528301900001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofMolecular Diversity
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectPhenylaminopyrimidines
dc.subject2-Arylimino-4-thiazolidinone derivatives
dc.subjectAnticancer agents
dc.subjectApoptosis
dc.subjectMolecular docking
dc.titleDesign, synthesis, and anticancer activity of novel 4-thiazolidinone-phenylaminopyrimidine hybrids
dc.typeArticle

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