QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP OF FLAVONOID INHIBITORS OF P56(LCK) PROTEIN-TYROSINE KINASE - A CLASSICAL QUANTUM CHEMICAL APPROACH/

QSAR studies on 104 flavonoid derivatives as p56(lck) protein tyrosine kinase inhibitors were performed, using classical and quantum chemica l parameters. The obtained results demonstrate in detail which specifi c electronic as well as hydrophobic and steric properties of the subst ituents play a significant role in their binding. The para and meta po sition in substituents at the 3' and 4' position of the phenyl ring sh ould have electron-donating properties and most probably this part of the flavonoid molecule interacts with the catalytic domain of the enzy me, through hydrogen bonds. The chromone moiety appears to be a mixed region indicating the dependence on hydrophobic (pi) and electronic pa rameters such as sum of charges at the chromone ring atoms Sigma delta (C3-C8). The steric hindrance of the substituent at C3 position in the chromone moiety is also a potency determining factor and a bulky grou p in this position has an adverse effect on the bioactivity in the ser ies.