Inhibition of wheat embryo calcium-dependent protein kinase by acridines and azaacridines

Abstract

The inhibition of wheat Ca 2+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 IC 50 values for wheat CDPK of less than 200,μM. Of these, effective compounds all have neutral or basic 4-substituents, except for 2,7-dibromo-4-carboxy-5-AAO (IC 50 73 μM), the carboxymethyl ester of which is a much better inhibitor (IC 50 20 μM). 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 (IC 50 1.5 μM), but the corresponding 4-substituted acridine analogue is a very poor inhibitor. Other potent inhibitors found include 1-nitro-4-P-8-AA (IC 50 4μM) and 7-bromo-4-methyl-5-AA (IC 50 0.7 μM). These potent and relatively specific CDPK inhibitors may be useful in obtaining evidence for CDPK involvement in plant cell responses to specific signals.