Protein Kinase Inhibitors in Plants of the Myrtaceae, Proteaceae, and Leguminosae

Abstract

Methanolic extracts of leaves, flowers, stems, bark, and other parts of representative plants of the Myrtaceae, specifically of the Eucalyptus, Melaleuca, Thryptomena, Callistomen, Acmena, and Angophora genera, variously contain high levels of inhibitors of plant Ca²⁺-dependent protein kinase (CDPK) and of Ca²⁺-calmodulin-dependent myosin light chain 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 ranged 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, Angophora, and Grevillea genera contained inhibitors of the catalytic subunit of the cyclic AMP-dependent protein kinase (cAK), inhibitor levels ranging from 20,000 to 9,600,000 PKIU (g FW)^-1. In general, cAK inhibitor levels found in the Myrtaceae were mostly much higher than levels of CDPK and MLCK inhibitors and reversed phase HPLC of such plant extracts revealed a multiplicity of components associated with cAK inhibitory activity. These in vitro screening procedures enable rapid detection and quantitation of levels of bioactive plant defence compounds with medicinal potential.

Protein kinase inhibitors - Eucalyptus - Melaleuca - Angophora - Grevillea - Thryptomena - Acmena - Callistomen - Myrtaceae - Proteaceae - Leguminosae