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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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Date
2017-11-01
Author
Cetin, Aysu
Celik Turgut, Gurbet
Disli, Ali
Yavuz, Serkan
Doyduk, Dogukan
Akdemir, ATİLLA
Yildirir, Yilmaz
Sen, Alaattin
Advisor
Type
Article
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Abstract
Cladribine (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.
Subject
Yavuz 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
URI
https://hdl.handle.net/20.500.12645/2024
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BEZMIALEM VAKIF UNIVERSITY

About us |Policies | Library | Contact us | Send Feedback | Sitemap | Admin

Bezmialem Vakıf Üniversitesi, Adnan Menderes Bulvarı Vatan Caddesi 34093 Fatih, İstanbul / TURKEY
Copyright © Bezmialem Vakıf Üniversitesi

Creative Commons Lisansı
Bezmialem Institutional Repository, Creative Commons Alıntı-GayriTicari-Türetilemez 4.0 Uluslararası Lisansı ile lisanslanmıştır.

OpenAccess@BVU

Support by  UNIREPOS