A study on the interaction between p60(c-Src) receptor tyrosine kinase and arylcarboxylic and arylacetic acid derivatives based on docking modes and in vitro activity

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ALTUNTAŞ T., Olgen S., Nebioglu D., Akaho E.

BIOLOGICAL & PHARMACEUTICAL BULLETIN, cilt.27, sa.1, ss.61-65, 2004 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 27 Sayı: 1
  • Basım Tarihi: 2004
  • Doi Numarası: 10.1248/bpb.27.61
  • Dergi Adı: BIOLOGICAL & PHARMACEUTICAL BULLETIN
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.61-65
  • Anahtar Kelimeler: arylacetic acid, arylcarboxylic acid, tyrosine kinase, molecular docking, INHIBITORS
  • Ankara Üniversitesi Adresli: Evet

Özet

The fundamental role that receptor tyrosine kinases play in cancer and other proliferative diseases has provided the impetus for an extensive effort on the part of both academic and pharmaceutical laboratories to develop highly specific inhibitors. In this study, inhibitory activity of previously synthesized arylacetic and arylcarboxylic acid derivatives were examined against substrate of tyrosine kinase. It can be assumed that the activity of compounds becomes higher when the -CH2 linkage exist between aromatic ring and the amide group of the side chain. In addition, when the R-1 and R-2 substitutents are methyl group in both series, the higher activity observed. The data obtained from docking study (DOCK4.0) indicated that compounds 2, 4, 7, 8, 11 render satisfactory interaction with the active site of enzyme, Lys295 of p60(c-Src) tyrosine kinase. Comparison of this interaction and the evaluation of biological data showed that compound 4 is the most active among the entire derivatives.