Cytotoxic pyrroloiminoquinones from four new species of South African latrunculid sponges.

Abstract

An examination of organic extracts of four new species of South African latrunculid sponges, Tsitsikamma pedunculata, T. favus, Latrunculia bellae, and Strongylodesma algoaensis, yielded 13 known and eight new pyrroloiminoquinone alkaloids, 3-dihydro-7,8-dehydrodiscorhabdin C (4), 14-bromo-3-dihydro-7,8-dehydrodiscorhabdin C (5), discorhabdin V (6), 14-bromo-1-hydroxydiscorhabdin V (7), tsitsikammamine A N-18 oxime (10), tsitsikammamine B N-18 oxime (11), 1-methoxydiscorhabdin D (12), and 1-aminodiscorhabdin D (13). Standard spectroscopic methods provided the structures of the pyrroloiminoquinone metabolites, while chiral GC-MS analysis of the acylated ozonolysis products of 21 confirmed the stereochemistry of the l-histidine residue in this compound. The anticancer activity of 20 pyrroloiminoquinone compounds was explored in the HCT-116 cancer cell line screen, and the DNA intercalation of the tsitsikammamines, together with their ability to cleave DNA through topoisomerase I inhibition, is discussed.

• Authors: Edith M Antunes, Denzil R Beukes, Michelle Kelly, Toufiek Samaai, Louis R Barrows, Kathryn M Marshall, Catherine Sincich, Michael T Davies-Coleman
• Journal: Journal of natural products (J Nat Prod) Vol. 67 Issue 8 Pg. 1268-76 (Aug 2004) ISSN: 0163-3864 [Print] United States
• PMID: 15332840 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Antineoplastic Agents
• Topoisomerase I Inhibitors
• Histidine

Topics

• Alkaloids (chemistry, isolation & purification, pharmacology)
• Animals
• Antineoplastic Agents (chemistry, isolation & purification, pharmacology)
• Drug Screening Assays, Antitumor
• Gas Chromatography-Mass Spectrometry
• HCT116 Cells
• Histidine (chemistry)
• Humans
• Molecular Structure
• Porifera (chemistry)
• South Africa
• Topoisomerase I Inhibitors