Synthesis and study of the cancer cell growth inhibitory properties of alpha-, gamma-tocopheryl and gamma-tocotrienyl 2-phenylselenyl succinates.
Vitamin E succinate selenium-conjugated molecules were synthesized and their apoptogenic properties were evaluated. 4-Methyl-2-phenylselenyl succinate (4) was prepared by the reaction of sodium benzeneselenolate with 2-bromosuccinic anhydrite in methanol solution. The methyl ester was converted to the acid (5) by hydrolysis with aqueous hydrochloric acid. Reaction of the 2-phenylselenyl succinic anhydrite (6) with alpha-tocopherol (1a), gamma-tocopherol (1c), and gamma-tocotrienol (2c) in acidic conditions gave the respective esters. The free radical scavenging properties of alpha-tocopheryl-2-phenylselenyl succinate (7), gamma-tocopheryl-2-phenylselenyl succinate (8), and gamma-tocotrienyl-2-phenylselenyl succinate (9) were evaluated in comparison with those of alpha-tocopheryl succinate (10), gamma-tocopheryl succinate (11), and gamma-tocotrienyl succinate (12), respectively, and the free tocopherols and gamma-tocotrienol. Compounds 7-9 induced a statistically significant decrease in prostate cancer cell viability compared to 10-12, respectively, or 5, exhibiting features of apoptotic cell death and associated with caspase-3 activation. These data show that structural modifications of vitamin E components by 5 enhance their apoptogenic properties in cancer cells.
Vraka
Panayiota S
PS
University of Cyprus, Department of Chemistry, 1678 Nicosia, Cyprus.
Drouza
Chryssoula
C
Rikkou
Maria P
MP
Odysseos
Andreani D
AD
Keramidas
Anastasios D
AD
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D024505:Tocopherols / Q000138:chemical synthesis* / Q000494:pharmacology*; D024508:Tocotrienols / Q000138:chemical synthesis* / Q000494:pharmacology*
D016166:Free Radical Scavengers; D024508:Tocotrienols; D024505:Tocopherols