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Structure‐Activity Comparison of the Cytotoxic Properties of Diethylmaleate and Chemical Analogs
Author(s) -
West James D,
Stamm Chelsea E
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.486.2
Subject(s) - chemistry , electrophile , maleic acid , molecule , lipophilicity , double bond , stereochemistry , biological activity , cytotoxic t cell , cytotoxicity , in vitro , biochemistry , organic chemistry , catalysis , copolymer , polymer
Molecules that contain α,β‐unsaturated carbonyls have a wide variety of uses in industry, molecular medicine, and biochemical research. Ester derivatives of maleic acid are commonly utilized to modify sulfhydryl groups within proteins due to their reactive (i.e., electrophilic) properties. In order to understand the effects of these maleic acid derivatives and structural analogs on cells, we have compared the cytotoxicities of diethylmaleate with molecules containing variations in the length of aliphatic chain linked to the ester bond as well as the type and orientation of the α, β‐bond that reacts with sulfhydryl groups. While each molecule that contains an electrophilic center causes apoptotic cell death in human RKO colorectal carcinoma cells, our results reveal significant differences in the cytotoxic potency of some molecules. Particularly, molecules that contain longer aliphatic chains linked to the ester bond are more potent at inducing cell death, as are molecules composed of a trans‐double bond (i.e., fumarate ester derivatives). Although the chemical rationale for the cellular effects of these molecules is still unclear, these results suggest that bond type, orientation, and lipophilicity have a pronounced influence on the cytotoxic potencies of electrophilic molecules containing α, β‐unsaturated carbonyls.