Evaluation of indole esters as inhibitors of p60(c-Src) receptor tyrosine kinase and investigation of the inhibition using receptor docking studies.
Several indole esters were tested as inhibitors of tyrosine kinase p60(c-Src). Compound (4) was found fairly active against the enzyme with IC50 = 1.34 microM. DOCK methodology was used to asses our inhibitors for their inhibitory potency against tyrosine kinase. The docking results showed that compounds (4), (25) and (26) were bound to the active site of the enzyme Lys 295 of p60(c-Src) tyrosine kinase. Both activity and docking studies showed a parallel result, with compound (4) having a better interaction with the enzyme active site and also greater activity than the other compounds, indicating a potential role as new lead inhibitor.
Faculty of Pharmaceutical Sciences and High Technology Research Institute, Kobe Gakuin University, 518 Arise, Ikawadani-cho, Nishiku, Kobe 651-2180, Japan. olgen@pharmacy.ankara.edu.tr
Sureyya
S
Olgen
Eiichi
E
Akaho
Dogu
D
Nebioglu
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D004952:Esters; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012984:Software; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D004952:Esters; D007211:Indoles; D016392:Proto-Oncogene Proteins pp60(c-src)