Drug release from functionalized oligodeoxynucleotide by photo-induced electron transfer.

We synthesized a photoreactive hairpin-type oligodeoxynucleotide (P-ODN) possessing an o-nitrobenzyl chromophore and a triplet quencher of 1-aminonaphthalene. Photoirradiation of the hybrid of H-ODN with its complementary DNA led to release of drug in an efficient amount, while the photo-induced drug release was remarkably suppressed in the absence of complementary DNA.

Synthesis and DNA cleavage reaction characteristics of enediyne prodrugs activated via an allylic rearrangement by base or UV irradiation.

A number of enediyne prodrugs 1-5 possessing an (E)-3-hydroxy-4-(2'-hydroxy-1'-phenylethylidene)cyclodeca-1,5-diyne scaffold have been synthesized via the Sonogashira coupling and an intramolecular Nozaki-Hiyama-Kishi reaction as the key steps. Upon incubation with enediyne prodrugs 4 and 5 possessing a free hydroxymethyl group on the exocyclic double bond, circular supercoiled DNA (Form I) underwent single strand cleavage into circular relaxed DNA (Form II) in buffer solution at pH 8.5, while the silylated analogs 1-3 showed very weak DNA cleavage activity.

Hypoxia-selective activation of 5-fluorodeoxyuridine prodrug possessing indolequinone structure: radiolytic reduction and cytotoxicity characteristics.

We synthesized a 5-fluorodeoxyuridine (5-FdUrd) derivative possessing an indolequinone structure (IQ-FdUrd) to characterize the radiolytic reduction in aqueous solution and the radiation-activated cytotoxicity against EMT6/KU cells under hypoxic conditions. IQ-FdUrd released antitumor agent 5-FdUrd upon hypoxic, but not aerobic, irradiation with the G value of 0.38 x 10(-7) mol J(-1).

In vitro and in vivo evaluation of novel antitumor prodrugs of 5-fluoro-2'-deoxyuridine activated by hypoxic irradiation.

Purpose: We previously developed a novel antitumor prodrug that has a 2-oxopropyl substituent at the N(1) position of 5-fluorouracil (5-FU) and releases 5-FU via one-electron reduction on hypoxic irradiation. Although the compound was effective in vivo, its activity against murine tumors was not high enough to warrant clinical studies. Therefore, we developed a similar family of radiation-activated prodrugs of 5-fluoro-2'-deoxyuridine (FdUrd), which is generally more potent than 5-FU, and investigated their radiation chemical reactivity and in vitro and in vivo effects.

One-electron reduction characteristics of N(3)-substituted 5-fluorodeoxyuridines synthesized as radiation-activated prodrugs.

We designed and synthesized N(3)-substituted 5-fluorodeoxyuridines as radiation-activated prodrugs of the antitumor agent, 5-fluorodeoxyuridine (5-FdUrd). A series of 5-FdUrd derivatives possessing a 2-oxoalkyl group at the N(3)-position released 5-FdUrd in good yield via one-electron reduction initiated by hypoxic irradiation. Cytotoxicity of the 5-FdUrd derivative possessing the 2-oxocyclopentyl group (3d) was low, but was enhanced by hypoxic irradiation resulting in 5-FdUrd release.