# FREE RADICAL METABOLITES IN QUINONE CONTAINING ANTITUMOR

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 1988 · $78,196

## Abstract

Free radical intermediates have been found in the metabolic pathways of a
wide variety of organic compounds including antitumor agents which contain
a quinone group.  Drug activity as well as toxic effects appear to be the
result of the purely chemical reactions that these free radicals can
undergo.  Our working hypothesis is that free radicals from quinone
containing antitumor agents are implicated in the agent's activity.  Before
free radical metabolism can be implicated in a given agent's activity
and/or toxicity, it is important that the chemistry of the free radical be
known, and that the free radical be found in the metabolic pathway or
generated by cells in culture.

We plan to continue to investigate the relationship of drug free radicals
to drug activity.  We found that the free radical generated by
electrochemical reduction of diaziquone (AZQ) is the same as that generated
by cancer cells in culture.  We were able to characterize the free radical
in terms of electron spin resonance parameters, electrochemical reduction
potentials and light spectroscopy.  These results put us now in a position
to study the chemical reactions of the AZQ free radical in the test tube
and be able to make biologically significant statements regarding the free
radical's behavior in vivo.  For instance, we are going to look at chemical
reactions of the free radicals of AZQ with nucleophiles of biological
interest such as GSH and also with DNA.  We want to relate their reaction
rates to drug activity.  We will also study the products of these reactions
as possible metabolites.

We and others have shown that for AZQ, borohydride reduction elicits DNA
strand breaks which cannot be found in the absence of reducing conditions.
We want to extend these experiments to in vitro and in vivo conditions
where the effect of reduced AZQ against murine leukemia P388 will be
investigated.  We were able to show that AZQ can be activated by visible
light (500 nm).  We are now ready to study the photoenhancement of AZQ
activity by visible light against cells in culture.

## Key facts

- **NIH application ID:** 3171477
- **Project number:** 5R01CA033681-05
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **SAM.gov UEI:** Z9CRZKD42ZT1
- **Principal Investigator:** PETER L. GUTIERREZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $78,196
- **Award type:** 5
- **Project period:** 1983-07-01 → 1990-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171477

## Citation

> US National Institutes of Health, RePORTER application 3171477, FREE RADICAL METABOLITES IN QUINONE CONTAINING ANTITUMOR (5R01CA033681-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171477. Licensed CC0.

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