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THE EFFECTS OF SOME IMIDAZOPYRAZINE DERIVATIVES ON TELOMERASE INHIBITION, MTDNA DAMAGE AND MTDNA COPY NUMBER

AYŞE GÜL MUTLU, ABDULKERİM BİLGİNER, ISMAİL KAYAĞİL, HÜLYA YILDIZ, ÜLKÜ BAYHAN, İNANÇ YILMAZ, ŞEREF DEMİRAYAK

Acta Pharmaceutica Sciencia - 2017;55(3):31-41

Mehmet Akif Ersoy University, Arts and Sciences Faculty, Department of Molecular Biology and Genetics, Burdur, Turkey

 

Imidazopyrazine derivatives have been studied for their curative effects on some diseases like cancer and neurological problems; also, some of these molecules have been patented. Primary human cells exhibit limited replicative potential but the cancer cells divided unlimitedly with passage in culture. This immortality is mainly a result of telomerase activity. We investigated the possible telomerase inhibitor effect and possible mtDNA damage action of five imidazopyrazine derivatives. Telomerase activities were measured by the PCR-ELISA based TRAP method and mtDNA damage assays were achieved by quantitative PCR. We used zebrafish as a model organism for our research. In the application of 6-(4-Metylphenyl-8-(4- chlorophenyl)imidazo[1, 2-a]pyrazine (C19H14N3Cl), it was determined that this compound inhibit telomerase activities to a statistically significant degree. The obtained results from molecular docking studies also supported the experimental results. Accordingly, this compound has the probability to be used as an anti-cancer agent after detailed studies.