In vitro antiproliferative and cytotoxic activities of novel kojic acid derivatives: 5-benzyloxy-2-selenocyanatomethyl- and 5-methoxy-2-selenocyanatomethyl-4-pyranone.

Abstract

Some kojic acid (KA) derivatives and selenium containing compounds possess antiproliferative properties. The present study tested novel selenocyanatomethyl derivatives of KA for growth inhibitory and LDH cytotoxic activities. Human skin carcinoma (A431) and human breast carcinoma (MCF7) cells were treated with 5-benzyloxy-2-selenocyanatomethyl-4-pyranone (P763) and 5-methoxy-2-selenocyanatomethyl-4-pyranone (P764) in selected concentrations for 24, 48 and 72 h. Cell viability tests aimed at intracellular injury of mitochondria (MTT) and lysosomes (neutral red uptake, NR) revealed (a) higher growth inhibitory activity of the benzyloxy-selenocyanatomethyl derivative of KA (P763) compared with the methoxy derivative (P764) in both cell lines, (b) an intensified effect with time of exposure (MTT test only). The results demonstrate that NR cell survival/viability assay is more sensitive than the MTT test to detect subcellular changes induced by test compounds. Cell membrane integrity determined by LDH leakage confirmed an exaggerated cytotoxic effect of P763 but similar sensitivity of both cell lines to membrane injury. The ED50 values for all three tests used indicate that injury of intracellular mitochondria and lysosomes precedes the loss of membrane integrity. Cell growth inhibitory activities of new selenium containing kojic acid derivatives are preferentially aimed at the intracellular compartment rather than the plasma membrane and enlarge the group of antiproliferative active compounds.

• Authors: Maria Fickova, Eliska Pravdova, Lars Rondhal, Michal Uher, Julius Brtko
• Journal: Journal of applied toxicology : JAT (J Appl Toxicol) Vol. 28 Issue 4 Pg. 554-9 (May 2008) ISSN: 0260-437X [Print] England
• PMID: 17879241 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2007 John Wiley & Sons, Ltd.

Chemical References

• 5-benzyloxy-2-selenocyanataomethyl-4-pyranone
• 5-methoxy-2-selenocyanatomethyl-4-pyranone
• Antineoplastic Agents
• Organoselenium Compounds
• Pyrones

Topics

• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Membrane (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Humans
• Inhibitory Concentration 50
• Lysosomes (drug effects)
• Mitochondria (drug effects)
• Organoselenium Compounds (pharmacology)
• Pyrones (pharmacology)
• Time Factors