Synthesis anticancer activity and molecular modeling of etodolac-thioether derivatives as potent methionine aminopeptidase (type II) inhibitors

dc.contributor.authorYelekçi, Kemal
dc.contributor.authorÇevik, Ozge
dc.contributor.authorYelekçi, Kemal
dc.contributor.authorDjikic, Teodora
dc.contributor.authorKüçükgüzel, Şükriye Güniz
dc.date.accessioned2019-06-27T08:05:51Z
dc.date.available2019-06-27T08:05:51Z
dc.date.issued2018
dc.departmentFakülteler, Mühendislik ve Doğa Bilimleri Fakültesi, Biyoinformatik ve Genetik Bölümüen_US
dc.description.abstractA series of (RS)-1-{[5-(substituted)sulfanyl-4-substituted-4H-124-triazole-3-yl]methyl}-18-diethyl-1349-tetrahydropyrano[34-b]indoles (5a-v) were designed and synthesized using a five-step synthetic protocol that involves substituted benzyl chlorides and (RS)-5-[(18-diethyl-1349-tetrahydropyrano[34-b]indole-1-yl)methyl]-4-substituted-24-dihydro-3H-124-triazole-3-thiones in the final step. The synthesized derivatives were evaluated for cytotoxicity and anticancer activity in vitro using the MTT (3-(45-dimethylthiazol-2-yl)-25-diphenyltetrazolium bromide) colorimetric method against VERO HEPG2 (human hepatocellular liver carcinoma) SKOV3 (ovarian carcinoma) MCF7 (human breast adenocarcinoma) PC3 and DU145 (prostate carcinoma) cells at 10(-5)M (10M) for 24h. Compounds 5d and 5h showed the best biological potency against the SKOV3 cancer cell line (IC50=7.22 and 5.10M respectively) and did not display cytotoxicity toward VERO cells compared to etodolac. Compounds 5k 5s and 5v showed the most potent biological activity against the PC3 cancer cell line (IC50=8.18 3.10 and 4.00M respectively) and did not display cytotoxicity. Moreover these compounds were evaluated for caspase-3 -9 and -8 protein expression and activation in the apoptosis pathway for 6 12 and 24h which play a key role in the treatment of cancer. In this study we also investigated the apoptotic mechanism and molecular modeling of compounds 5k and 5v on the methionine aminopeptidase (type II) enzyme active site in order to get insights into the binding mode and energy.en_US]
dc.identifier.citation20
dc.identifier.doi10.1002/ardp.201700195en_US
dc.identifier.issn0365-6233en_US
dc.identifier.issn1521-4184en_US
dc.identifier.issn0365-6233
dc.identifier.issn1521-4184
dc.identifier.issue43558
dc.identifier.pmid29575045en_US
dc.identifier.scopus2-s2.0-85044374082en_US
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://hdl.handle.net/20.500.12469/1125
dc.identifier.urihttps://doi.org/10.1002/ardp.201700195
dc.identifier.volume351en_US
dc.identifier.wosWOS:000428990000001en_US
dc.identifier.wosqualityN/A
dc.institutionauthorYelekçi, Kemalen_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.journalMaster Journal List Surveyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAnticancer activityen_US
dc.subjectApoptosisen_US
dc.subjectEtodolacen_US
dc.subjectMolecular dockingen_US
dc.subjectThioethersen_US
dc.titleSynthesis anticancer activity and molecular modeling of etodolac-thioether derivatives as potent methionine aminopeptidase (type II) inhibitorsen_US
dc.typeArticleen_US
dspace.entity.typePublication
relation.isAuthorOfPublication9407938e-3d31-453b-9199-aaa8280a66c5
relation.isAuthorOfPublication.latestForDiscovery9407938e-3d31-453b-9199-aaa8280a66c5

Files