A promising redox cycle-based strategy for designing a catechol-type diphenylbutadiene as a potent prooxidative anti-melanoma agent

Abstract

Developing anti-melanoma agents with increased activity and specificity is highly desirable due to the increasing incidence, highly metastatic malignancy, and high mortality rate of melanoma. Abnormal redox characteristics such as higher levels of tyrosinase, NAD(P)H: quinone oxidoreductase-1 (NQO1) and reactive oxygen species (ROS) observed in melanoma cells than in other cancer cells and normal cells illustrate their redox vulnerability and have opened a window for developing prooxidative anti-melanoma agents (PAAs) to target the vulnerability. However, how to design PAAs which promote selectively the ROS accumulation in melanoma cells remains a challenge. This work describes a promising redox cycle-based strategy for designing a catechol-type diphenylbutadiene as such type of PAA. This molecule is capable of constructing an efficient catalytic redox cycle with tyrosinase and NQO1 in melanoma B16F1 cells to induce selectively the ROS (mainly including hydrogen peroxide, H₂O₂) accumulation in the cells, resulting in highly selective suppression of melanoma B16F1 cells over tyrosinase-deficient HeLa and normal L-02 cells.

Keywords: Hydrogen peroxide; NQO1; Prooxidant; Redox; Tyrosinase.