Kynurenines with Neuroactive and Redox Properties: Relevance to Aging and Brain Diseases

Table 2

Kynurenines with redox behavior.

Metabolite	Chemical structure*	Reactive species generated	Reactive species scavenged	References
TRP	pKa (COOH) = 2.38; pKa (NH2) = 9.34	O2^•−, H2O2, ^∙OH.; Increases GSH, TBARS, and DCF fluorescence. Decreases catalase activity.	ONOO^− and ^∙OH.; Chemiluminometric assays.	[239–241]
KYN	pKa (COOH) = 1.9; pKa (anilino group) = 5.1; pKa (NH2) = 8.5	H2O2, OH^∙, ONOO^−.; Reduces chemiluminescence induced by H2O2.  Prevents lipid peroxidation and fluorescence of DCF.	O2^•−, H2O2.; Cytochrome c reduction.	[56, 60, 62, 242]
KYNA	pKa (COOH) < 2; pKa (N) = 3.65; pKa (OH) = 13.9	Potentiates the prooxidants properties of 𝛿-aminolevulinic acid [83, 216].	OH^∙, ONOO^−, O2^•−.; Reduces degradation of 2-desoxyribose in synthetic systems.; Reduces TBARS and fluorescence of DCF and prevents protein degradation.	[79, 84, 243–245]
ANA	pKa (COOH) = 2.17; pKa (NH3^+) = 4.85	^∙OH.; Creates a complex with copper, increasing Fe reactivity in Fenton reaction.	^∙OH.; Creates a complex with copper and captures radicals in inflammatory processes.	[130, 131]
3-HK	pKa (COOH) = 1.9; pKa (alpha NH2) = 9.6	O2^•−, H2O2.; Reaction with peroxidase. Induces H2O2 accumulation and generates cell death.	ROO^∙, O2^•−.; Prevents oxidation of B-phycoerythrin. Decreases lipid peroxidation.	[59, 88, 101, 246]
XA	pKa (N) = 1.8; pka (OH1) = 7.3; pKa (OH2) = 12.3	O2^•−, ^∙OH, O^1.; Generates ROS through complex with Fe ions. Inactivates aconitase. Generates O2^•−, upon irradiation.	^∙OH.; Prevents oxidation of ABTS from hematoxylin oxidation.; Inhibits lipid peroxidation in low density lipoprotein.; Protects NADP isocitrate from oxidation.	[106, 112, 115]
3-HA	pKa (NH2) = 5.19; pKa (OH) = 10.12	O2^•−, H2O2.; Anthraniloyl radical (semiquinone) generated during autooxidation. Inhibits oxygen uptake by mitochondria.	ROO^∙.; Acts as coantioxidant with alpha-tocopherol. Prevents lipid peroxidation.	[118, 119, 124, 247]
PIC	pKa (N) = 1.03; pKa (COOH) = 5.40	^∙OH.; Chelates Fe^2+ and enhances Fenton reaction.	Chelates different bivalent metals as Ni^2+, Zn^2+, Cb^2+, Cu^2+, and Pb^2+.	[143, 147]
QUIN	pKa (COOH) = 2.43; pKa (COOH) = 4.78	^∙OH.; Chelates Fe^2+ and enhances Fenton reaction. Generates ROS via excitotoxicity.		[162]

∗The chemical structures were built with the program ACD/ChemSketch Freeware (http://www.acdlabs.com/resources/freeware/chemsketch/).