Designing dichlorobinaphthoquinone as a prooxidative anticancer agent based on hydrogen peroxide-responsive in situ production of hydroxyl radicals.

Abstract Compared with normal cells, cancer cells harbor increased levels of reactive oxygen species (ROS) including hydrogen peroxide (H 2 O 2), and therefore are more vulnerable to further ROS production. This biochemical difference favors the idea of developing new powerful selective prooxidative anticancer agents. However, it still remains a challenge to design them by targeting this difference. Herein, we report the designed dichlorobinaphthoquinone as a prooxidative anticancer agent which is capable of exploiting increased levels of H 2 O 2 of cancer cells to produce in situ lethal hydroxyl radicals (HO•) and thereby kill them selectively, a design strategy inspired from Zhu et al.'s work on the molecular mechanism for metal-independent production of HO•. Graphical abstract Image 1 Highlights • Designing prooxidative anticancer agents by metal-independent production of HO•. • BQ-DC was designed based on the skeleton of natural conocurvone. • Preferential killing of cancer cells over normal cells by the designed BQ-DC. • BQ-DC can exploit increased levels of H 2 O 2 of cancer cells to in situ produce HO•. • The H 2 O 2 -responsive formation of HO• was evidenced by a series of experiments. [ABSTRACT FROM AUTHOR]