INHIBITION OF WHEAT EMBRYO CALCIUM-DEPENDENT PROTEIN-KINASE BY ACRIDINES AND AZAACRIDINES

The inhibition of wheat Ca2+-dependent protein kinase (CDPK) by substituted acridines and substituted 5-, 6-, 7- and 8-azaacridines (5-AA, 6-AA, 7-AA and 8-AA) was examined. Of a total of 71 substituted acridines and azaacridines examined, only 20 have IC50 values for wheat CDPK of less than 200 mu M. Of these, effective compounds all have neutral or basic 4-substituents, except for 2,7-dibromo-4-carboxy-5-AAO (IC50 73 mu M), the carboxymethyl ester of which is a much better inhibitor (IC50 20 mu M). There is a large aza position effect so that various 4-substituted azaacridines can be either very active or very poor inhibitors depending upon the azaacridine nucleus substituted. One of the most potent inhibitors found is the 8-AA 4-N-(2-dimethylaminoethyl)carboxamide (4-P) derivative (IC50 1.5 mu M), but the corresponding 4-substituted acridine analogue is a very poor inhibitor. Other potent inhibitors found include 1-nitro-4-P-8-AA (IC50 4 mu M) and 7-bromo-4-methyl-5-AA (IC50 0.7 mu M). These potent and relatively specific CDPK inhibitors may be useful in obtaining evidence for CDPK involvement in plant cell responses to specific signals.