Riboflavin as a bioorthogonal photocatalyst for the activation of a Pt^IV prodrug

Abstract

Riboflavin acts as bioorthogonal photocatalyst to activate a PtIV anticancer prodrug in the biological environment.

Catalysis Concepts in Medicinal Inorganic Chemistry

“…Our group has recently proposed ap aradigms hift, devising an innovative prodrug photoactivation strategy (Figure 7) where metal complexes are unconventionally employed as substrates. [64] Aw ide range of metal-based agentsc an serve as substrates in catalytic reactions and their efficient and selective light activation may help reducing some of the unwanted biological effects characteristic of metallodrugs. Catalytic transformations of metal complexes remainu pt od ate practicallyu nknown.…”

“…In the last two years,w ed emonstrated that flavins, including flavoproteins, are capable to perform photocatalytic transformations of Pt IV and Ru II -arene prodrug complexes in biologi-cal environments (Figure 7). [64][65][66] In this new type of catalysis, the rich photoredoxc hemistry of flavins triggersm etal reduction and ligand dissociation reactions in the Pt IV and Ru II complexes, respectively.P t IV and Ru II -arene complexes are families of anticancerc ompounds that have shown promising features as chemotherapeutic agentsu pon light activation,y et they have poor absorption properties ando ften require damaging UVAl ight for triggering the formation of their biologically active species. According to our current comprehension of the catalysis mechanism,t he active catalysti st he two-electron-reduced flavin generated by the photooxidation of electrondonorm olecules.…”

Bioorthogonal Catalytic Activation of Platinum and Ruthenium Anticancer Complexes by FAD and Flavoproteins

“…Light activation of the riboflavin–prodrug pair triggers cisplatin‐related antiproliferative activity in PC3 cancer cells 11. Unlike in classic organometallic catalysis, where metals act as catalysts, in this reaction, the metal complex is an unconventional substrate,12 and the biocompatible riboflavin acts as catalyst.…”

“…Therefore, novel strategies to prompt their photochemistry at longer wavelengths are pivotal for their use in photochemotherapy. Complexes 1 – 5 are stable towards hydrolysis in the dark, and have either no or poor photoreactivity under blue light excitation 11, 17, 18…”

“…Three concentrations (0.2, 2, and 20 m m ) of MES (as buffer, pH 6) or NADH in phosphate buffer (PB, pH 7, 100 m m ) were employed for this purpose. MES was selected as an electron donor to follow up our previous work on riboflavin11 while NADH was chosen for its relevance as a biological cofactor in numerous reactions catalyzed by flavoenzymes 19. Moreover, metal‐based catalytic drugs have been recently shown to kill cancer cells by interfering with cellular NAD + /NADH homeostasis 20, 21, 22…”