The discovery of chimeric anti-melanoma agents is reported. These molecules are potent growth suppressors of melanoma cells
in vitro
with growth inhibition of 50% (GI
50
) values as low as 1.32 µM. Compounds were more toxic to melanoma cells
in vitro
than commonly used anti-melanoma agent dacarbazine as measured by TUNEL assay. They induced both caspase-independent apoptosis evident by colocalization of TUNEL with endonuclease G (EndoG) and caspase-mediated apoptosis measured by colocalization of TUNEL with caspase-activated DNase (CAD). In addition, compounds
3
and
5
strongly induced oxidative injury to melanoma cells as measured by TUNEL colocalization with heme oxygenase-1 (HO1). Dacarbazine induced only caspase-independent apoptosis, which may explain why it is less cytotoxic to melanoma cells than compounds
3
,
4
and
5
.