title: Free radical scavenging and antioxidative activity of melatonin derivatives.
abstract: This article describes the synthesis and antioxidative properties of melatonin derivatives. Tryptamines and cysteinyl or mercaptopropionyl derivatives were deliberately condensed with coupling reagents to give melatonin derivatives 4a-d and 5a, b. The preliminary evaluation indicated that compound 4c showed improved scavenging activity compared with vitamin C (IC50 43 microM vs 65 microM, where IC50 is the concentration of the test compound that induced a change of 50% in absorbance during the 30 min observation) on diphenyl-p-picrylhydrazyl (DPPH) tests. Derivative 5b, which possesses the thiolactyl moiety, showed moderate potency compared with melatonin (IC50 235 microM vs 690 microM) in the H(2)O(2) scavenging test. Intriguingly, 4c displayed 2-fold more potency than melatonin (IC50 51 microM vs 125 microM) in scavenging NO in the macrophage model. These results suggested that the cysteinyl-conjugated derivative 4c may be a suitable lead to further optimize potent antioxidants for certain oxidative stress conditions.
authors.affiliation: School of Pharmacy, National Defense Medical Center, 161 Minchuan East Road, Section 6, Taipei 114, Taiwan.
authors.forename: Pen-Lin
authors.initials: PL
authors.lastname: Tsia
authors.forename: Ming-Kuan
authors.initials: MK
authors.lastname: Hu
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D004347:Drug Interactions; D006861:Hydrogen Peroxide / Q000737:chemistry; D008550:Melatonin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D006861:Hydrogen Peroxide; D008550:Melatonin