Mechanism of action of the third generation benzopyrans and evaluation of their broad anti-cancer activity in vitro and in vivo.
Alexander J Stevenson, Eleanor I Ager, Martina A Proctor, Dubravka Škalamera, Andrew Heaton, David Brown, Brian G Gabrielli
Scientific Reports | Published : 2018
Successive rounds of chemical modification in three generations of benzopyran molecules have shown to select for different mechanisms of actions and progressive increases in anti-cancer activity. In this study, we investigated the mechanism of action of the third-generation benzopyran compounds, TRX-E-002-1 and TRX-E-009-1. High-content screening of a panel of 240 cancer cell lines treated with TRX-E-009-1 demonstrated it has broad anti-cancer potential. Within this screen, melanoma cell lines showed a range of sensitivities and subsequently a second independent panel of 21 melanoma 3D spheroid lines were assessed for their responses to both TRX-E-002-1 and TRX-E-009-1 compounds. Time-lapse ..View full abstract