N-acyl-3,5-bis(arylidene)-4-piperidones and related compounds which stimulate fyn kinase.
This study is part of a long term project designed to explore the hypothesis that stimulation of cancer cells followed by treatment with one or more cytotoxic agents may create greater damage to tumours than to the corresponding normal tissues. The aim of the present investigation was to discover various compounds which stimulate a protein tyrosine kinase, namely fyn kinase. The N-acyl-3,5-bis(arylidene)-4-piperidones and related analogues activated this enzyme using concentrations of 25 microM while representative molecules achieved this result at 0.1 microM. Molecular modelling suggested that the compounds interact transiently with the ATP binding site of fyn kinase thereby enhancing the catalytic phosphorylation of proteins. In the future, candidate antineoplastic agents will be designed which incorporate the structural features of these enzyme stimulators with the goal of their being formed in vitro and in vivo prior to the release of cytotoxins.
Das
Umashankar
U
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5C9, Canada.
Selvakumar
Ponniah
P
Sharma
Rajendra K
RK
Haas
Thomas A
TA
Dimmock
Jonathan R
JR
D000255:Adenosine Triphosphate / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology; D001665:Binding Sites; D002384:Catalysis; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010766:Phosphorylation; D010881:Piperidones / Q000737:chemistry* / Q000494:pharmacology; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D010881:Piperidones; D000255:Adenosine Triphosphate; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases