A comparative analysis of the photosensitized inhibition of growth-factor regulated protein kinases by hypericin-derivatives

The photodynamic inhibitory effect of hypericin and a number of hypericin-derivatives were investigated in vitro using numerous growth-factor regulated protein kinases including receptor-bound (Insulin-R, EGF-R) and non-receptor (Lyn, c-Fgr, CSK, Syk) protein tyrosine kinases as well as Ser/Thr (PK-C, protein kinase CK-2, CK-1) protein kinases. Modification of the hypericin structure altered significantly the specificity of the protein kinase inhibition. In particular, methylation or attachment of long lipophilic chains to both methyl groups of the hypericin molecule strongly enhanced the specificity toward PK-C. (C) 1996 Academic Press, Inc.