# ANALOGS OF 6-VINYLURACIL AS ANTITUMOR AGENTS

> **NIH NIH R01** · MONTEFIORE MEDICAL CENTER (BRONX, NY) · 1991 · $155,524

## Abstract

This program is aimed at the synthesis and antitumor evaluation of a
series of 6-alkenyluracils, and is intended to amplify and extend the
earlier findings that 6-vinyluracil and 6-(2-bromoethylacrylyl)-uracil
are active in vivo against a number of experimental tumors in mice.  It
is highly likely that these lead compounds function as alkylating agents,
although there seems to be no clear-cut relationship between the rate at
which the derivatives prepared to date react with cysteine and their in
vitro growth inhibitory activity.  It is now proposed to examine
compounds with a much wider range of substituent groups, with the overall
goal of developing compounds with enhanced levels of antitumor activity.
Specifically, two classes of compounds are proposed.  Class A is
comprised of the free pyrimidine bases; pyrimidine nucleosides bearing
unsaturated groups at C-6, such as 6-vinyluridine; and compounds where
the double bond forms part of another ring.  Class B consists of
pyrimidine cyclonucleosides in which an alkene moiety comprises the
bridging system.  As far as is possible, the selection of compounds for
synthesis will be guided by the results of biological evaluation.  It is
suggested that the nucleoside targets might have a different spectrum of
activity relative to the free bases by virtue of differences in their
uptake and distribution.
     The target compounds will be evaluated for their ability to inhibit
the growth of mouse and human tumor cells in vitro.  Several types of
assays will be used, including growth inhibition of mouse L1210 and P388
leukemias, and human HL-60 leukemia cell in suspension culture; a
clonogenic assay using HT-29 human colon carcinoma cells; and by a
colorimetric assay (MTT) using a number of human lung carcinoma cell
lines.  The in vitro work will be done in-house under the supervision of
Dr. E. L. Schwartz.  Compounds with significant activity in the cell
culture screens will be examined for in vivo activity in mice bearing
leukemias or solid tumors.  The in vivo work will be done at Memorial
Sloan-Kettering Cancer Center.  The ability of selected nucleosides of
class A to act as inhibitors or substrates of nucleoside phosphorylases
will be determined by Dr. M. el Kouni of Brown University, RI. in
nucleosides have been shown recently to bind to uridine phosphorylase.
The nucleosides of class A, which are expected to adopt the syn
conformation, might therefore be inhibitors if they alkylate a
nucleophilic site on the enzyme.

## Key facts

- **NIH application ID:** 3174138
- **Project number:** 2R01CA036517-07A1
- **Recipient organization:** MONTEFIORE MEDICAL CENTER (BRONX, NY)
- **SAM.gov UEI:** FP1VD1HU5HV7
- **Principal Investigator:** BRIAN A OTTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $155,524
- **Award type:** 2
- **Project period:** 1984-07-01 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174138

## Citation

> US National Institutes of Health, RePORTER application 3174138, ANALOGS OF 6-VINYLURACIL AS ANTITUMOR AGENTS (2R01CA036517-07A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174138. Licensed CC0.

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