Kinetin & Kinetin Analogues as Substrates & Inhibitors of Xanthine Oxidase

Cytokinin interaction with free radical metabolism and senescence: Effects on endogenous lipoxygenase and purine oxidation

“…The first stage of the research involved the application of a system comprising of xanthine and xanthine oxidase, which generates FR's, and the checking of Hpoxygenase levels. The second stage followed the kinetics of an in vitro combination of CK and XO and the possible formation of a 2,8 dihydroxy-purine, as suggested by Henderson et al (1962) and Leopold and Kriedemann (1975). The third stage of the research testing the amine-amide hypothesis compared the senescence retarding action of benzyl adenine (0-NH-CHR), an amine, to that of the amide benzoyl adenine "…”

“…However, the above results may be reinterpreted not as a direct effect of CK scavenging but rather, as suggested by Leopold and Kriedemann (1975), as a "braking mechanism of CK upon its own oxidation". The latter would occur by specific inhibition of xanthine oxidase by formation of a 2,8 dihydroxypurine compound (Henderson et al 1962). The pertinence in plants of purine breakdown to allantoic acid, including the step where X reacting with XO forms uric acid and FR's, has been pointed out in detail elsewhere (Leopold and Kriedemann 1975, Leshem et al 1981, Schlee et al 1966.…”

Inhibitors of Xanthine Oxidase: Scaffold Diversity and Structure‐Based Drug Design

“…The natural purine adenine ( 10 , IC 50 =75.61 μ m ) has been found to exhibit similar inhibitory activity to allopurinol against XO with a competitive mechanism . The molecule is oxidized by the enzyme, and its product is more active than the parent compound . In 1968 Baker and Kozma identified irreversible XO inhibitors in derivatives of 8‐(benzylthio)adenine 11 .…”

“…[39] The molecule is oxidized by the enzyme,a nd its product is more active than the parent compound. [40] In 1968 Baker and Kozma [37] identified irreversible XO inhibitors in derivatives of 8-(benzylthio)adenine 11.O ne of the most potent inhibitors was adenine analogue 11 a.S ubstituents on the exocyclica mino group produced active purine analogues,w ith 12 (IC 50 = 0.45 mm)b eing more than 150-fold more potent than adenine itself. [39c] The novel compound 12 was also tested with respect to the mechanism of electron transfer in the enzyme, and wasf ound to perform better than allopurinol, as it did not generate ROS.Allopurinol produced hydrogen peroxide by transferring two electrons to the enzyme, while 12 didn ot react in this manner.…”

The Cytokinins

“…Thus, for example, Letham lists promotion of protein, RNA, lipid, and starch synthesis among the long list of other more specific effects (4). Cytokinins have been reported to stimulate production of tyramine methyltransferase in barley roots (38), to inhibit certain glycolytic kinases (39), and to be substrates for xanthine oxidase (40). Apparent decreases in enzyme activity in the hexose monophosphate shunt without concomitant decreases in the activity of glycolytic enzymes have been noted with high (10-5M) concentrations of kinetin (41).…”