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

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dc.contributor.authorTÜRE, ASLI
dc.contributor.authorsTure, Asli; Ergul, Mustafa; Ergul, Merve; Altun, Ahmet; Kucukguzel, Ilkay
dc.date.accessioned2022-03-12T22:41:47Z
dc.date.available2022-03-12T22:41:47Z
dc.date.issued2021
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.identifier.doi10.1007/s11030-020-10087-1
dc.identifier.eissn1573-501X
dc.identifier.issn1381-1991
dc.identifier.pubmed32328961
dc.identifier.urihttps://hdl.handle.net/11424/236163
dc.identifier.wosWOS:000528301900001
dc.language.isoeng
dc.publisherSPRINGER
dc.relation.ispartofMOLECULAR DIVERSITY
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectPhenylaminopyrimidines
dc.subject2-Arylimino-4-thiazolidinone derivatives
dc.subjectAnticancer agents
dc.subjectApoptosis
dc.subjectMolecular docking
dc.subjectIN-VITRO EVALUATION
dc.subjectBIOLOGICAL EVALUATION
dc.subjectKINASE INHIBITORS
dc.subjectTYROSINE KINASE
dc.subjectNONNUCLEOSIDE INHIBITORS
dc.subjectANTIMICROBIAL ACTIVITY
dc.subject4-THIAZOLIDINONES
dc.subjectDERIVATIVES
dc.subjectANTITUBERCULOSIS
dc.subjectMECHANISM
dc.titleDesign, synthesis, and anticancer activity of novel 4-thiazolidinone-phenylaminopyrimidine hybrids
dc.typearticle
dspace.entity.typePublication
local.avesis.idbf22f9a5-55e5-4a3b-8754-afecaadc889d
local.import.packageSS17
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages26
local.journal.quartileQ2
oaire.citation.endPage1050
oaire.citation.issue2
oaire.citation.startPage1025
oaire.citation.titleMOLECULAR DIVERSITY
oaire.citation.volume25
relation.isAuthorOfPublication515da16e-3e07-453b-bfbb-c60fbd768648
relation.isAuthorOfPublication.latestForDiscovery515da16e-3e07-453b-bfbb-c60fbd768648

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