The effects of some imidazopyrazine derivatives on telomerase inhibition, mtDNA damage and mtDNA copy number

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Mutlu A. G., Bilginer A., Kayağil I., Yıldız H., Bayhan Ü., Yılmaz İ., ...More

Acta Pharmaceutica Sciencia, vol.55, no.3, pp.31-41, 2017 (Scopus) identifier

  • Publication Type: Article / Article
  • Volume: 55 Issue: 3
  • Publication Date: 2017
  • Doi Number: 10.23893/1307-2080.aps.05517
  • Journal Name: Acta Pharmaceutica Sciencia
  • Journal Indexes: Scopus
  • Page Numbers: pp.31-41
  • Keywords: Anticancer drugs, Imidazopyrazine derivatives, mtDNA copy number, mtDNA damage, Telomerase inhibition
  • Istanbul Medipol University Affiliated: Yes

Abstract

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.