Synthesis, Pharmacokinetic Characterization and Antioxidant Capacity of Carotenoid Succinates and Their Melatonin Conjugates
Dalma Czett,
Katalin Böddi,
Veronika Nagy,
Anikó Takátsy,
József Deli,
Paul Tone,
György T. Balogh,
Anna Vincze,
Attila Agócs
Affiliations
Dalma Czett
Department of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary
Katalin Böddi
Department of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary
Veronika Nagy
Department of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary
Anikó Takátsy
Department of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary
József Deli
Department of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary
Paul Tone
Department of Medicine, Richmond University Medical Center, Staten Island, NY 10310, USA
György T. Balogh
Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111 Budapest, Hungary
Anna Vincze
Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111 Budapest, Hungary
Attila Agócs
Department of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary
Carotenoid succinates were synthesized from hydroxy carotenoids and were coupled to a commercially available derivative of melatonin via amide bond for producing more powerful anti-oxidants and yet new hybrid lipophilic bifunctional molecules with additional therapeutic effects. The coupling reactions produced conjugates in acceptable to good yields. Succinylation increased the water solubility of the carotenoids, while the conjugation with melatonin resulted in more lipophilic derivatives. The conjugates showed self-assembly in aqueous medium and yielded relatively stable colloidal solutions in phosphate-buffered saline. Antioxidant behavior was measured with ABTS and the FRAP methods for the carotenoids, the carotenoid succinates, and the conjugates with melatonin. A strong dependence on the quality of the solvent was observed. TEAC values of the new derivatives in phosphate-buffered saline were found to be comparable to or higher than those of parent carotenoids, however, synergism was observed only in FRAP assays.
