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

The inhibition of wheat Ca2+-dependent protein kinase (CDPK) by substi tuted 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 acridin es 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 inhib itors depending upon the azaacridine nucleus substituted. One of the m ost potent inhibitors found is the 8-AA 4-N-(2-dimethylaminoethyl)carb oxamide (4-P) derivative (IC50 1.5 mu M), but the corresponding 4-subs tituted acridine analogue is a very poor inhibitor. Other potent inhib itors found include 1-nitro-4-P-8-AA (IC50 4 mu M) and 7-bromo-4-methy l-5-AA (IC50 0.7 mu M). These potent and relatively specific CDPK inhi bitors may be useful in obtaining evidence for CDPK involvement in pla nt cell responses to specific signals.