Vitamin E analogues as inducers of apoptosis: structure-function relation
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Author(s)
Birringer, M
EyTina, JH
Salvatore, BA
Neuzil, J
Griffith University Author(s)
Year published
2003
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Recent results show that alpha-tocopheryl succinate (alpha-TOS) is a proapoptotic agent with antineoplastic activity. As modifications of the vitamin E (VE) molecule may affect its apoptogenic activity, we tested a number of newly synthesised VE analogues using malignant cell lines. Analogues of alpha-TOS with lower number of methyl substitutions on the aromatic ring were less active than alpha-TOS. Replacement of the succinyl group with a maleyl group greatly enhanced the activity, while it was lower for the glutaryl esters. Methylation of the free succinyl carboxyl group on alpha-TOS and delta-TOS completely prevented the ...
View more >Recent results show that alpha-tocopheryl succinate (alpha-TOS) is a proapoptotic agent with antineoplastic activity. As modifications of the vitamin E (VE) molecule may affect its apoptogenic activity, we tested a number of newly synthesised VE analogues using malignant cell lines. Analogues of alpha-TOS with lower number of methyl substitutions on the aromatic ring were less active than alpha-TOS. Replacement of the succinyl group with a maleyl group greatly enhanced the activity, while it was lower for the glutaryl esters. Methylation of the free succinyl carboxyl group on alpha-TOS and delta-TOS completely prevented the apoptogenic activity of the parent compounds. Both Trolox and its succinylated derivative were inactive. alpha-tocotrienol (alpha-T3 H) failed to induce apoptosis, while italic gamma-T3 H was apoptogenic, and more so when succinylated. Shortening the aliphatic side chain of italic gamma-T3 by one isoprenyl unit increased its activity. Neither phytyl nor oleyl succinate caused apoptosis. These findings show that modifications of different functional moieties of the VE molecule can enhance apoptogenic activity. It is hoped that these observations will lead to the synthesis of analogues with even higher apoptogenic and, consequently, antineoplastic efficacy.
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View more >Recent results show that alpha-tocopheryl succinate (alpha-TOS) is a proapoptotic agent with antineoplastic activity. As modifications of the vitamin E (VE) molecule may affect its apoptogenic activity, we tested a number of newly synthesised VE analogues using malignant cell lines. Analogues of alpha-TOS with lower number of methyl substitutions on the aromatic ring were less active than alpha-TOS. Replacement of the succinyl group with a maleyl group greatly enhanced the activity, while it was lower for the glutaryl esters. Methylation of the free succinyl carboxyl group on alpha-TOS and delta-TOS completely prevented the apoptogenic activity of the parent compounds. Both Trolox and its succinylated derivative were inactive. alpha-tocotrienol (alpha-T3 H) failed to induce apoptosis, while italic gamma-T3 H was apoptogenic, and more so when succinylated. Shortening the aliphatic side chain of italic gamma-T3 by one isoprenyl unit increased its activity. Neither phytyl nor oleyl succinate caused apoptosis. These findings show that modifications of different functional moieties of the VE molecule can enhance apoptogenic activity. It is hoped that these observations will lead to the synthesis of analogues with even higher apoptogenic and, consequently, antineoplastic efficacy.
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Journal Title
British Journal of Cancer
Volume
88
Issue
12
Copyright Statement
© The Author(s) 2003. From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
Subject
Oncology and carcinogenesis