# CAMPTOTHECIN ANALOGS AS TUMOR INHIBITORS

> **NIH NIH R01** · RESEARCH TRIANGLE INSTITUTE · 1989 · $158,782

## Abstract

The finding of high antitumor activity of 9-aminocamptothecin (9-
AC) suggests the preparation of a number of other 9-substituted
compounds which we have reason to believe will have high
activity in L1210 mouse leukemia.  These include the 9-cyano,
9,10-methylene dioxy, and 9-hydroxy analogs.  In order to extend
the clinical applicability of our most active camptothecin
compounds which are water insoluble, we propose to prepare
water soluble analogs which in many cases would be acting as pro-
drugs for the parent compound, such as the 21-glycinate esters of
9- or 10-AC, certain water soluble esters of 9- or 10- hydroxy-1a
or water soluble amides of 9- or 10 AC.  Whether the pyridine
nitrogen in ring B and the pyridone moiety in ring D are required
for activity will be ascertained by synthesis of analogs 1b and 2,
which have the same shape and size of camptothecin.  An analog
with much different shape such as 3 will also be prepared and
tested in vitro and in vivo.  A major study will be conducted to
ascertain whether the same structural requirements for in vivo
antitumor activity of 1a apply also to the interference of 1a with
topoisomerase (Topo I) function in biochemical systems and to
determine whether drug action on Topo I is responsible for the
observed antitumor activity.  In this connection, the mechanism
of inhibition of Topo I by 1a and analogs, the production of
protein-associated strand breaks with selected key 1a analogs, and
the sites of drug-induced trapping of DNA-Topo I cleavage
complexes to the genome will be studied.  These studies will be
facilitated by the preparation of radiolabeled camptothecin and
one or two key analogs.

## Key facts

- **NIH application ID:** 3177588
- **Project number:** 5R01CA038996-05
- **Recipient organization:** RESEARCH TRIANGLE INSTITUTE
- **SAM.gov UEI:** JJHCMK4NT5N3
- **Principal Investigator:** MONORE E WALL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $158,782
- **Award type:** 5
- **Project period:** 1984-12-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177588

## Citation

> US National Institutes of Health, RePORTER application 3177588, CAMPTOTHECIN ANALOGS AS TUMOR INHIBITORS (5R01CA038996-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177588. Licensed CC0.

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