Enzymatic activation of indolequinone-substituted 5-fluorodeoxyuridine prodrugs in hypoxic cells. Issue 11 (1st June 2019)

• Record Type: Journal Article
• Authors: Jiho, Yota; Kurihara, Ryohsuke; Kawai, Kiyohiko; Yamada, Hisatsugu; Uto, Yoshihiro; Tanabe, Kazuhito
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 11(2019)
• Page Start: 1304
• Page End: 1307
• Publication Date: 2019-06-01
• Subjects: Enzymatic activation -- Prodrug -- Tumor hypoxia -- Reductase; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.04.003
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Among the various enzymes, reductases that catalyze one-electron reduction are involved in the selective activation of functional compounds or materials in hypoxia, which is one of the well-known pathophysiological characteristics of solid tumors. Enzymatic one-electron reduction has been recognized as a useful reaction that can be applied in the design of tumor hypoxia-targeting drugs. In this report, we characterized the enzymatic reaction of 5-fluorodeoxyuridine (FdUrd) prodrug bearing an indolequinone unit (IQ-FdUrd), which is a substrate of reductases. IQ-FdUrd was activated to release FdUrd under hypoxic conditions after treatment with cytochrome NADPH P450 reductase. We also confirmed that IQ-FdUrd showed selective cytotoxicity in hypoxic tumor cells.