Apoptosis Induced by 2-ArylBenzothiazoles-MediatedPhotodynamic Therapy in Melanomas via Mitochondrial Dysfunction.

A mildand efficient synthetic development of 2-arylbenzothiazoles 5mediated by ceric ammonium nitrate (CAN) via intramolecularcyclization of N-phenyl-thiobenzamides 4was achieved. Further compounds 5were reduced to correspondingamines 6, and their photodynamic therapy (PDT) effectwas evaluated on malignant human melanoma A375 cells. Amine 6lplus ultraviolet A (UVA) induced caspase-3 activity, poly(ADP-ribose)polymerasecleavage, M30 positive CytoDeath staining, and subsequent apoptoticcell death. Our data disclosed that treatment of A375 cells with 6lplus UVA resulted in a decrease in mitochondrial membranepotential (ΔΨmt), oxidative phosphorylationsystem (OXPHOS) subunits, and adenosine triphosphate (ATP) but anincrease in mitochondrial DNA 4977-bp deletion via reactive oxygenspecies (ROS) generation. Transmission electron microscopy (TEM) observationsalso showed major ultrastructural alterations of mitochondria. Additionally, 6lplus UVA was also shown to reduce murine melanoma sizein a mouse model. The present study supports the hypothesis that 6l-PDT may serve as a potential ancillary modality for thetreatment of melanoma. [ABSTRACT FROM AUTHOR]