Protein tyrosine kinase (PTK) inhibitors represent emerging therapeutics for cancer chemoprevention. In
our study, hematoxylin (26) was identified as one of the most remarkable c-Src inhibitors in an orthogonal
compound-mixing library (32200 compounds) by using an ELISA-based automated high-throughput screening
(HTS) strategy. Interestingly, hematoxylin was found to be an ATP competitive broad-spectrum PTK inhibitor
in vitro, with IC50 values ranging from nanomolar to micromolar level. Further studies showed that such
inhibition was associated with the PTK phosphorylation and subsequent downstream signaling pathways.
The structure-activity relationship assessment of the PTK inhibitory potency of hematoxylin analogues
isolated from Heamatoxylon campechianum was in good agreement with the result of concurrent molecular
docking simulation: the catechol moiety in ring A and the hematoxylin-like three-dimensional structure
were essential for c-Src-targeted activities. Hematoxylin and its natural analogues were substantially validated
to function as a new class of PTK inhibitors