1. ¹German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany
2. ²Peptides & Elephants Gmbh, Potsdam-Rehbrücke, Germany
3. ³Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, USA
4. ⁴Department of Pathology II, Faculty of Health Sciences, University Hospital, Linköping, Sweden
5. ⁵School of Health Sciences, Griffith University, Southport, Queensland, Australia

Correspondence: Dr J Neuzil, School of Health Sciences, Griffith University Gold Coast Campus, Southport, 9726 Queensland, Australia. E-mail: j.neuzil@mailbox.gu.edu.au

Received 30 September 2002; Revised 11 March 2003; Accepted 18 March 2003.

Abstract

Recent results show that -tocopheryl succinate (-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 -TOS with lower number of methyl substitutions on the aromatic ring were less active than -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 -TOS and -TOS completely prevented the apoptogenic activity of the parent compounds. Both Trolox and its succinylated derivative were inactive. -tocotrienol (-T3 H) failed to induce apoptosis, while -T3 H was apoptogenic, and more so when succinylated. Shortening the aliphatic side chain of -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.