Evaluation of Cancer-preventive Activity and Structure-activity Relationships of 3-demethylubiquinone Q2, Isolated from the Ascidian Aplidium Glabrum, and Its Synthetic Analogs

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2005 Dec 2

PMID 16320003

Citations 20

Authors

Sergey N Fedorov

Oleg S Radchenko

Larisa K Shubina

Nadezhda N Balaneva

Ann M Bode

Valentin A Stonik

Zigang Dong

Affiliations

Soon will be listed here.

Abstract

Purpose: 3-Demethylubiquinone Q2 was isolated from the ascidian Aplidium glabrum. The cancer-preventive properties and the structure-activity relationship for 3-demethylubiquinone Q2 and 12 of its synthetic analogs are reported.

Methods: Compounds, having one or several di- or triprenyl substitutions and quinone moieties with methoxyls in different positions, were synthesized. The cancer-preventive properties of compounds and were tested in JB6 Cl41 mouse skin cells, using a variety of assessments, including the methanethiosulfonate (MTS) assay, flow cytometry, and soft agar assay. Statistical nonparametric methods were used to confirm statistical significance.

Results: All quinones tested were shown to inhibit JB6 Cl41 cell transformation, to induce apoptosis, AP-1, and NF-kappaB activity, and to inhibit p53 activity. The most promising effects were indicated for compounds containing two isoprene units in a side chain and a methoxyl group at the para-position to a polyprenyl substitution.

Conclusions: Quinones and demonstrated cancer-preventive activity in JB6 Cl41 cells, which may be attributed to the induction of p53-independent apoptosis. These activities depended on the length of side chains and on the positions of the methoxyl groups in the quinone part of the molecule.

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