PROTEIN-KINASE INHIBITORS IN PLANTS OF THE MYRTACEAE, PROTEACEAE, ANDLEGUMINOSAE

Methanolic extracts of leaves, flowers, stems, bark, and other parts o f representative plants of the Myrtaceae, specifically of the Eucalypt us, Melaleuca, Thryptomena, Callistomen, Acmena, and Angophora genera, variously contain high levels of inhibitors of plant Ca2+-dependent p rotein kinase (CDPK) and of Ca2+-calmodulin-dependent myosin light cha in kinase (MLCK). In terms of the protein kinase inhibition unit (PKIU ), defined as the amount in the standard protein kinase assays causing 50 % inhibition of protein kinase activity, these inhibitor levels ra nged from the non-detectable to 179,000 PKIU (gram fresh weight)-1 [(g FW)-1] and there was no consistent pattern of inhibitor distribution. A variety of other plants tested had low or non-detectable levels of CDPK and MLCK inhibitors. Plants of the Eucalyptus, Melaleuca, Angopho ra, and Grevillea genera contained inhibitors of the catalytic subunit of the cyclic AMP-dependent protein kinase (cAK), inhibitor levels ra nging from 20,000 to 9,600,000 PKIU (g FW)-1. In general, cAK inhibito r levels found in the Myrtaceae were mostly much higher than levels of CDPK and MLCK inhibitors and reversed phase HPLC of such plant extrac ts revealed a multiplicity of components associated with cAK inhibitor y activity. These in vitro screening procedures enable rapid detection and quantitation of levels of bioactive plant defence compounds with medicinal potential.