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Synthesis and Functional Investigations of Computer Designed Novel Cladribine-Like Compounds for the Treatment of Multiple Sclerosis

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dc.contributor.authorYavuz, Serkan
dc.contributor.authorCetin, Aysu
dc.contributor.authorAkdemir, ATİLLA
dc.contributor.authorDoyduk, Dogukan
dc.contributor.authorDisli, Ali
dc.contributor.authorCelik Turgut, Gurbet
dc.contributor.authorSen, Alaattin
dc.contributor.authorYildirir, Yilmaz
dc.contributor.institutionauthorAKDEMİR, ATİLLA
dc.date.accessioned2019-10-05T13:21:48Z
dc.date.available2019-10-05T13:21:48Z
dc.date.issued2017-11-01
dc.description.abstractCladribine (2-CdA) is used as an anti-cancer drug but is currently studied as a potential treatment for use in relapsing-remitting multiple sclerosis (MS). In this study, we computer designed, synthesized, and characterized two novel derivatives of 2-CdA, K1-5d and K2-4c, and investigated their underlying mechanism of beneficial effect using the CCRF-CEM and RAJI cell lines. For this purpose, we first determined their effect on MS and DNA damage and repair-related gene expression profiles using custom arrays along with 2-CdA treatment at non-toxic doses. Then, we determined whether cells underwent apoptosis after treatment with 2-CdA, K1-5d, and K2-4c in CCRF-CEM and RAJI cells, using the DNA fragmentation assay. It was found that both derivatives modulated the expression of the pathway-related genes that are important in inflammatory signaling, apoptosis, ATM/ATR, double-strand break repair, and the cell cycle. Furthermore, 2-CdA, K1-5d, and K2-4c significantly activated apoptosis in both cell lines. In summary, our data demonstrate that although both derivatives act as anti-inflammatory and apoptotic agents, inducing the accumulation of DNA strand breaks and activating the ultimate tumor suppressor p53 in T and B lymphocytes, the K1-5d derivative has shown more promising activities for further studies.
dc.description.sponsorshipTürkiye Bilimsel Ve Teknolojik Araştırma Kurumu ( Tübitak )
dc.identifier
dc.identifier.citationYavuz S., Cetin A., Akdemir A., Doyduk D., Disli A., Celik Turgut G., Sen A., Yildirir Y., -Synthesis and Functional Investigations of Computer Designed Novel Cladribine-Like Compounds for the Treatment of Multiple Sclerosis-, ARCHIV DER PHARMAZIE, cilt.350, 2017
dc.identifier.doi10.1002/ardp.201700185
dc.identifier.pubmed28960496
dc.identifier.scopus85030470615
dc.identifier.urihttps://hdl.handle.net/20.500.12645/2024
dc.identifier.wosWOS:000414337000005
dc.language.isoen
dc.titleSynthesis and Functional Investigations of Computer Designed Novel Cladribine-Like Compounds for the Treatment of Multiple Sclerosis
dc.typeArticle
dspace.entity.typePublication
local.article.journalnameTürkiye Klinikleri Pediatri Dergisi
local.avesis.id30eeeddb-5331-44c3-860e-545fe0f6247c
local.avesis.response1894
local.publication.goal03 - Sağlık ve Kaliteli Yaşam
local.publication.isinternational1
relation.isAuthorOfPublication19bc513a-c695-4e72-ba1d-83b8d6c574c8
relation.isAuthorOfPublication.latestForDiscovery19bc513a-c695-4e72-ba1d-83b8d6c574c8
relation.isGoalOfPublication9c198c48-b603-4e2f-8366-04edcfc1224c
relation.isGoalOfPublication.latestForDiscovery9c198c48-b603-4e2f-8366-04edcfc1224c
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