Picolinic Acid Derivatives Research Articles

Catechol 2,3-Dioxygenase-catalyzed Synthesis of Picolinic Acids from Catechols

Various picolinic acid derivatives were synthesized from ammonia and hydroxymuconic semialdehyde derivatives that were oxidatively prepared from various catechols by the action of Pseudomonas catechol 2,3-dioxygenase (C23O, metapyrocatechase).

A Short Synthesis of Fusaric Acid and Analogues

Abstract Fusaric acid (5-n-butyl-pyridine-2-carboxylic acid) and other substituted picolinic acid derivatives are synthesized in two steps from readily available α,β-unsaturated hydrazones and 2-chloroacrylonitrile in high yield.

Synthesis, structure, and spectral characteristics of copper complexes with picolinic acid derivatives

1. Treatment of chloropicolinic acids with aqueous solutions of various copper salts in alcohol media results in the formation of complexes of composition 2∶1. 2. The structures of the newly synthesized complexes have been shown to be identical in the solid state and in solution. 3. Diverse modes of coordination of picolinic acid derivatives have been demonstrated; this may be one of the factors responsible for the ease of formation of metallocomplexes in biological systems, and thus may be responsible for the high biological activity (of picolinic acid derivatives).

Ca2+-mediated activation of phosphoenolpyruvate carboxykinase occurs via release of Fe2+ from rat liver mitochondria.

The addition of calcium chloride to rat liver homogenates resulted in activation of phosphoenolpyruvate carboxykinase by as much as 50%. The enhanced activity was inhibited by quinolinic acid; it was not additive with activation by FeCl2, and stimulation was prevented by 1,10-phenanthroline. Activation by calcium was lost when the particulate fractions of liver were removed, but an activating system could be reconstituted with isolated mitochondria, purified P-enolpyruvate carboxykinase, and purified ferroactivator. Iron-loaded mitochondria were more responsive to calcium than controls. A release of Fe2+ from washed mitochondria could be detected spectrophotometrically when 25-75 nmol of Ca/mg of protein were added to the mitochondrial suspension. If Ca2+ was buffered with ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, the threshold of Ca2+ necessary for release of Fe2+ was approximately 10(-7) M, with peak response between 5 X 10(-7) and 10(-6) M. Total Fe2+ detected was normally 20-30 pmol of Fe2+/mg of protein. The synthetic activator of P-enolpyruvate carboxykinase, 3-aminopicolinic acid, as well as other picolinic acid derivatives, is capable of withdrawing Fe2+ associated with the mitochondrial fraction; after incubation with mitochondria, 3-aminopicolinate will activate phosphoenolpyruvate carboxykinase in the absence of exogenous metal.

Structural requirements for pyridine carboxylate effects on phosphoenolpyruvate carboxykinase

It has previously been established that quinolinic acid and 3-mercaptopicolinic acid cause hypoglycemia by inhibiting Phosphoenolpyruvate (PEP) carboxykinase and gluconeogenesis. In the rat, 3-aminopicolinic acid permits Fe 2+ to activate this enzyme; it enhances gluconeogenesis and causes hyperglycemia. In the present study, other pyridine carboxylates were screened for effects on the activity of PEP carboxykinase. The structural requirement for an inhibitor or an activator of this enzyme has been defined: It must be a picolinic acid derivative with the α carboxyl unsubstituted and with another group on position 3. The group at position 3 determines the effect (inhibition or activation) and the potency of the compound. Compounds such as picolinic acid, all the isomers of quinolinic acid, 2-mercaptonicotinic acid, and 2-aminonicotinic acid were inactive. Fe 2+ enhances the potency of quinolinate and 2-mercaptopicolinate 15- to 20-fold, and 3-aminopicolinate does not activate the carboxykinase in the absence of Fe 2+. It is therefore assumed that Fe 2+ binds to the ring nitrogen and the α-carboxyl group of one or more molecules of these compounds to form an effective coordination complex. Complexes involving picolinate derivatives with an acidic function at position 3 inhibit; the complex of Fe 2+ with 3-aminopicolinate either delivers Fe 2+ to the catalytic site and then dissociates or the Fe 2+ in the complex is catalytically active. 3-Aminopicolinate causes hyperglycemia in the guinea pig. It activates guinea pig liver cytosolic PEP carboxykinase in vitro but does not activate the mitochondrial carboxykinase. If activation of PEP carboxykinase is the means by which 3-aminopicolinate causes hyperglycemia, our findings indicate that the cytosolic enzyme can play an important role in glucose synthesis in species having appreciable amounts of both carboxykinases.

Transition metal eight-coordination. 8. Stereochemical integrity, geometrical isomers, and isomerization of mixed ligand tungsten(IV) chelates containing picolinic acid and 8-quinolinol derivatives

Transition metal eight-coordination. 8. Stereochemical integrity, geometrical isomers, and isomerization of mixed ligand tungsten(IV) chelates containing picolinic acid and 8-quinolinol derivatives

Inhibition of Dopamine β-Hydroxylase in Blood Vessels by Picolinic Acid Derivatives in vivo and their Antihypertensive Effects

The effect of picolinic acid derivatives, 5-butylpicolinic (fusaric) acid (FA), 5-(3′,4′-dibromobutyl)picolinic acid(Br2FA)and 5-(N-N-dimethyldithiocarbamoilmethyl) picolinic acid (YP-279) on dopamine β-hydroxylase in blood vessels in vivo was studied. Maximum inhibition of the conversion of 14C-dopamine(14C-DA) to 14C-norepinephrine (14C-NE) in rat aorta, mesenteric artery and renal artery was detected 30 min after FA and Br2FA (75 mg/kg) and 60 min after YP-279 (75 mg/kg). NE synthesis from 14C-DA returned to near control values by 6 hr in the blood vessels. NE levels of the aorta and mesenteric artery were significantly reduced by 30 to 50% at 4 hr after Br2FA or FA (75 mg/kg). Dopamine β-hydroxylase (DBH) activity, using tyramine as substrate, in heart, aorta, mesenteric artery and renal artery was markedly reduced. The concentrations of FA, Br2FA and YP-279 in rat blood following a single i.p. injection of each drug increase rapidly, reaching highest values in 0 to 30 min and decreasing slowly to 0 after 6 hr. These compounds did not affect the uptake of 3H-NE into the rat heart. These three compounds were found to lower blood pressure effectively in normal Wistar rats (above 25 mg/kg).

The effects of some alpha picolinic acid derivatives on growth and sporulation of bacilli

The effects of ethyl picolinate and picolinamide on growth and sporulation of B. megaterium and B. subtilis have been studied in synthetic medium containing glucose. Ethyl picolinate inhibits sporulation probably by undergoing hydrolysis intracellularly, the acid produced chelating with some metal essential for utilization of the neutral intermediates. Picolinamide gives heat labile spores but the mechanism does not appear to be metal chelation. Picolinamide may interfere with the role of dipicolinic acid as an activator of NADH 2 oxidase. Different sites of action of alpha picolinic acid, its ester and amide have been proposed.

A Picolinic Acid Derivative: A Plant Growth Regulator

4-Amino-3,5,6-trichloropicolinic acid is more toxic to many broad-leaved plants than 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid. It is comparable in absorption by foliage, in translocation, and in soil-leaching characteristics; in soil, however, it retains its activity for a longer time.