AMK is an active metabolite of the neurohormone melatonin .1,2,3,4It is formed from melatoninviathe metabolic intermediate AFMK that is then deformylated by catalase or formamidase.5,6AMK scavenges singlet oxygenin vitrowhen used at a concentration of 200 μM.1It inhibits the epinephrine- and arachidonic acid-induced production of prostaglandin E2and PGD2in ovine seminal vesicle microsomes in a concentration- and time-dependent manner, as well as LPS-induced increases in COX-2 levels in RAW 264.7 macrophages when used at a concentration of 500 μM.2,3AMK (20 mg kg) decreases MPTP-induced increases in lipidperoxidation in the cytosol and mitochondria from substantia nigra and striatum in a mouse model of MPTP-induced Parkinson’s disease.4 1.Schaefer, M., and Hardeland, R.The melatonin metabolite N1-acetyl-5-methoxykynuramine is a potent singlet oxygen scavengerJ. Pineal Res.46(1)49-52(2009) 2.Kelly, R.W., Amato, F., and Seamark, R.F.N-acetyl-5-methoxy kynurenamine, a brain metabolite of melatonin, is a potent inhibitor of prostaglandin biosynthesisBiochem. Biophys. Res. Commun.121(1)372-379(1984) 3.Mayo, J.C., Sainz, R.M., Tan, D.-X., et al.Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophagesJ. Neuroimmunol.165(1-2)139-149(2005) 4.Tapias, V., Escames, G., López, L.C., et al.Melatonin and its brain metabolite N1-acetyl-5-methoxykynuramine prevent mitochondrial nitric oxide synthase induction in parkinsonian miceJ. Neurosci. Res.87(13)3002-3010(2009) 5.Tan, D.-X., Manchester, L.C., Reiter, R.J., et al.Melatonin directly scavenges hydrogen peroxide: A potentially new metabolic pathway of melatonin biotransformationFree Radic. Biol. Med.29(11)1177-1185(2000) 6.Hirata, F., Hayaishi, O., Tokuyama, T., et al.In vitro and in vivo formation of two new metabolites of melatoninJ. Biol. Chem.249(4)1311-1313(1974)
6(5H)-Phenanthridinone is an inhibitor of poly(ADP-ribose) polymerase 1 (PARP1) and PARP2. It decreases radiation-induced PARP activity and proliferation of RDM4 murine lymphoma cells. 6(5H)-Phenanthridinone reduces NF-κB-induced transcription of the genes encoding TNF-α, IL-2, and IFN-γ in rat lymphocytes. In vivo, 6(5H)-phenanthridinone reduces spinal cord expression of inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, IL-2, and IFN-γ and reduces disease score in a rat model of experimental autoimmune encephalomyelitis (EAE). It also decreases serum levels of lactate dehydrogenase as well as hepatic lipidperoxidation, oxidative DNA damage, and PARP levels.
9c(i472) is an inhibitor of 15-lipoxygenase-1 (15-LO-1; IC50 = 0.19 μM).1 It decreases LPS- and IFN-γ-induced NF- B activity in RAW-Blue cells when used at concentrations of 0.2, 1, and 5 μM. 9c(i472) reduces LPS- and IFN-γ-induced increases in Nos2 expression and lipidperoxidation in RAW 264.7 cells when used at a concentration of 5 μM.