Synthesis and anticancer effects of some novel 2-(4-phenoxyphenyl)-1H-benzimidazole derivatives on K562 cell line

Gurkan-Alp A. S., GÖKER A. H., ALP M., ÖZKAN T., SUNGUROĞLU A.

ARCHIVES OF PHARMACAL RESEARCH, cilt.38, sa.5, ss.650-658, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 38 Sayı: 5
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1007/s12272-014-0438-x
  • Dergi Adı: ARCHIVES OF PHARMACAL RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.650-658
  • Anahtar Kelimeler: Anticancer activity, Benzimidazole, CML, K562, Apoptosis, COMET ASSAY, BIOLOGICAL EVALUATION, INDUCED APOPTOSIS, AGENTS, 1H-BENZIMIDAZOLES, BENZIMIDAZOLES
  • Ankara Üniversitesi Adresli: Evet

Özet

A series of novel 2-(4-phenoxyphenyl)-1H-benzimidazole derivatives was synthesized and tested in vitro on human chronic myelogenous leukemia (CML) cell line K562. Benzimidazoles containing 5-amidino (10), 5-N-isopropylamidino (11), 5-bromo (13), and 5,6-dimethyl (14) derivatives exhibited remarkable cytotoxic activity. The quantitative analysis of apoptosis by flowcytometry demonstrated that the percentages of early and late apoptotic K562 cells treated with these compounds were significantly higher than cells without treatment. We also investigated the effects of these compounds on the expression of apoptosis-related genes BAX, BCL-2, BAD and BIM. Treatment of K562 cells wih compounds 10-14 significantly increased the expression levels of the proapoptotic genes BAX, BAD and BIM, whereas compound 20 increased BAX and BAD.