Studies in Marine Natural Product Synthesis, Isolation and Ecology
type: CreativeWork
description: Previous studies indicated the marine pyridoacridone alkaloid ascididemin possessed a unique biological profile. Investigation of synthetic routes to ascididemin led to the discovery that ascididemin precursors possessed a wide range of biological activities. One precursor possessed hollow fiber in vivo antitumoral activity and continuing in vivo studies at the NCI, using subcutaneous xenograft assays, are in progress. A crystal structure of a precursor indicates that these tetracyclic heterocycles are planar, suggesting intercalation as a mechanism of antitumoral action. Ascididemin was synthesized by two novel ring E forming reactions. The superior methodology was also useful in the preparation of analogues, such as kuanoniamine A. Ascididemin possessed promising hollow fiber in vivo antitumoral activity but was poorly active in a subcutaneous xenograft study. Ascididemin was incapable of exerting antitumoral activity at a distance and further analogues were prepared to address this problem. Ten analogues were prepared, with all the non-bromine containing analogues selected for in vivo evaluation at the NCI. Two ring A analogues were prepared by a thennew synthetic route, including the antiviral natural product 11-hydroxyascididemin. 11-Methoxyascididemin was selected for hollow fiber evaluation. Two bromine containing ring D analogues were prepared, including the antifungal natural product 2-bromoleptoclinidinone. A crystal structure on 2-bromoleptoclinidinone was the first determined on a pyridoacridone alkaloid and the molecule was planar, further supporting an intercalative mechanism of action. Due to non-selective antitumoral cytotoxicity, ring D analogues are not useful antitumoral agents. Six carbon-based ring E analogues were prepared by novel methodology. All 6-substituted analogues assessed were selected for in vivo antitumoral evaluation. Hollow fiber antitumoral activity decreased with bulk of the substituent. 6-Methylascididemin has been selected for …
abstract: Previous studies indicated the marine pyridoacridone alkaloid ascididemin possessed a unique biological profile. Investigation of synthetic routes to ascididemin led to the discovery that ascididemin precursors possessed a wide range of biological activities. One precursor possessed hollow fiber in vivo antitumoral activity and continuing in vivo studies at the NCI, using subcutaneous xenograft assays, are in progress. A crystal structure of a precursor indicates that these tetracyclic heterocycles are planar, suggesting intercalation as a mechanism of antitumoral action. Ascididemin was synthesized by two novel ring E forming reactions. The superior methodology was also useful in the preparation of analogues, such as kuanoniamine A. Ascididemin possessed promising hollow fiber in vivo antitumoral activity but was poorly active in a subcutaneous xenograft study. Ascididemin was incapable of exerting antitumoral activity at a distance and further analogues were prepared to address this problem. Ten analogues were prepared, with all the non-bromine containing analogues selected for in vivo evaluation at the NCI. Two ring A analogues were prepared by a thennew synthetic route, including the antiviral natural product 11-hydroxyascididemin. 11-Methoxyascididemin was selected for hollow fiber evaluation. Two bromine containing ring D analogues were prepared, including the antifungal natural product 2-bromoleptoclinidinone. A crystal structure on 2-bromoleptoclinidinone was the first determined on a pyridoacridone alkaloid and the molecule was planar, further supporting an intercalative mechanism of action. Due to non-selective antitumoral cytotoxicity, ring D analogues are not useful antitumoral agents. Six carbon-based ring E analogues were prepared by novel methodology. All 6-substituted analogues assessed were selected for in vivo antitumoral evaluation. Hollow fiber antitumoral activity decreased with bulk of the substituent. 6-Methylascididemin has been selected for …
author: Lindsay, Brent Steven
language: en
license: https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm
date published: 1998
date modified: 2026-07-24T01:02:59Z
provider: University of Auckland
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: ResearchSpace@Auckland

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2292/509