Marine spongian sesquiterpene phenols, dictyoceratin-C and smenospondiol, display hypoxia-selective growth inhibition against cancer cells.

Abstract

In the course of our search for hypoxia-selective growth inhibitors against cancer cells, a sesquiterpene phenol, dictyoceratin-C (1), was isolated from the Indonesian marine sponge of Dactylospongia elegans under the guidance of the constructed bioassay. Dictyoceratin-C (1) inhibited proliferation of human prostate cancer DU145 cells selectively under hypoxic condition in a dose-dependent manner at the concentrations ranging from 1.0 to 10 μM. The subsequent structure-activity relationship study using nine sesquiterpene phenol/quinones (2-10), which were isolated from marine sponge, was executed. We found that smenospondiol (2) also exhibited the similar hypoxia-selective growth inhibitory activity against DU145 cells, and the para-hydroxybenzoyl ester moiety would be important for hypoxia-selective growth inhibitory activity of 1. In addition, the mechanistic analysis of dictyoceratin-C (1) revealed that the 10 μM of 1 inhibited accumulation of Hypoxia-Inducible Factor-1α under hypoxic condition.

• Authors: Masayoshi Arai, Takashi Kawachi, Hiroki Sato, Andi Setiawan, Motomasa Kobayashi
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 24 Issue 14 Pg. 3155-7 (Jul 15 2014) ISSN: 1464-3405 [Electronic] England
• PMID: 24865416 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Hydroxybenzoates
• Phenols
• Sesquiterpenes
• dictyoceratin-C
• smenospondiol

Topics

• Animals
• Antineoplastic Agents (chemistry, isolation & purification, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Humans
• Hydroxybenzoates (chemistry, isolation & purification, pharmacology)
• Hypoxia (metabolism)
• Molecular Conformation
• Neoplasms (drug therapy, metabolism, pathology)
• Phenols (chemistry, isolation & purification, pharmacology)
• Porifera (chemistry)
• Sesquiterpenes (chemistry, isolation & purification, pharmacology)
• Structure-Activity Relationship