Design, synthesis and docking studies of benzimidazole derivatives as potential EGFR inhibitors

ÇELİK İ., KILCIGİL G., GÜVEN B., Kara Z., Gurkan-Alp A. S., KARAYEL A., ...Daha Fazla

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, cilt.173, ss.240-249, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 173
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1016/j.ejmech.2019.04.012
  • Dergi Adı: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Index Chemicus (IC)
  • Sayfa Sayıları: ss.240-249
  • Anahtar Kelimeler: Benzimidazole, Thiosemicarbazide, Triazole, Thiadiazole, EGFR inhibitory activity, X-ray, Docking, TYROSINE KINASE INHIBITORS, ANTIOXIDANT PROPERTIES, LUNG-CANCER, AGENTS
  • Ankara Üniversitesi Adresli: Evet

Özet

In this study, a series of benzimidazoles bearing thiosemicarbazide chain or triazole and thiadiazole rings were designed and synthesized. Crystal and molecular structure of the compound 5c has been characterized by single crystal X-ray crystallographic analysis. EGFR kinase inhibitory potencies of synthesized compounds were compared with erlotinib in vitro and most of the compounds exhibited significant activities. Cell culture studies were also carried out for selected compounds and 12b was found to be the most active compound. To understand the binding mode of synthesized benzimidazoles, three compounds (12b, 16, 16c) were selected and placed on the binding site of EGFR tyrosine kinase based on their kinase inhibitor potencies and cell culture studies. Docking study indicated that compound 12b showed two-hydrogen bonding interactions with residues of LYS721 and THR830 at the binding pocket. (C) 2019 Elsevier Masson SAS. All rights reserved.