Reduction of quaternary benzophenanthridine alkaloids by NADH and NADPH

Abstract

Spectroscopic techniques have shown that quaternary benzophenanthridine alkaloid~ (sanguinarine (Ia). chelerythrine (Ie), sanguilutine (If), sanguirubine (Ie), chelirubine (Ib), and cheli1utine (Id» are reduced by NADH or NADPH to their dihydro forms. The formation of the oxidized form of a coenzyme was demonstrated by HPLC. The kinetics of the reaction of sanguinarine with NADH has been studied rather in detail; the reaction was found to be reversible. its stoichiometry was 1 : 1. Reactivity of the tested alkaloids toward the coenzymes was given by reactivity of the imine bond. This was graded like pK values for the formation of the corresponding pseudobases and correlated with the energy of the lowest unoccupied molecular orbital of these compounds. The possible biological and pharmacological importance of the studied reactions is discussed.The quaternary benzophenanthridine alkaloids I a -If occur in various species of the families Papaveraceae, Fumariaceae, and Rutaceae l • These substances affect the metabolic processes in bacteria or animals and can act as, e.g., antibacterial, antitubular or antitumour substances 2 -6. The effects of these substances in vivo are closely related to their interactions with important macromolecular compounds of cells, especially with certain enzymes, such as NaJK -ATPase 7 , choline esterases 8 • 9 , and amino transferases lO • Interactions of these substances with biopolymers depend on their chemical reactivityll.12. The substances can readily react with -.sH groups of proteins and low-molecular-weight compounds, get converted (in moderately alkaline media) to pseudo-bases II, and can quite easily be reduced to the corresponding dihydro compounds III. All these reactions occur on the imine bond of the substances (Scheme 1), which is a natural site for attack by nucleophilic groups ref. 12 ).The objective of this paper is to describe the reactions of these substances with NADH and NADPH, i.e., with the reduced forms of nicotinamide adenine dinucleotide coenzymes present in considerable quantities in all cells. These reactions may be metabolically important in the parent plants and in the bacterial or animal cells, where these substances get as drugs.Collection Czechoslovak Chern. Commun. (VOI~ 51] (1986]

Structural studies of benzophenanthridine alkaloid free bases by NMR spectroscopy

“…1h: Fagaronine: literature: chelerythrine (1a) 19 9.00, sanguilutine (1b) 19 8.80, chelirubine (1c) 19 7.70, chelilutine (1d) 19 8.50, sanguirubine (1e) 19 7.90, sanguinarine (1f) 19 8.05, nitidine (1g) 20 12.10 and fagaronine (1h) 11 13.20 (7.57 OH). Upon addition of Na 2 CO 3 (a pH of 11.8-11.9 was determined for a 9 : 1 mixture of DMSO and a saturated aqueous solution of Na 2 CO 3 ), the alkaloids of the sanguinarine type (1a-f) were completely converted into the corresponding free bases.…”

Palmatine and Berberine Isolation Artifacts

“…One of the reasons for this lower stability may be the higher p K values of protoberberines. For comparison, the p K values of benzophenanthridines are roughly 7.5−9.0 (in H 2 O), the p K of berberine is 15.4, and the p K of palmatine is 15.7 (in MeOH). Despite this lower stability, we managed to determine the chemical shifts of both 2a and 2b in CD 2 Cl 2 and C 6 D 6 (Tables −4).…”

A liquid chromatographic–mass spectrometric evidence of dihydrosanguinarine as a first metabolite of sanguinarine transformation in rat

“…In blood and organs, the equilibrium between these forms depends mainly upon the pH. The iminium bond in SA is susceptible to nucleophilic addition (of mainly SH-compounds) and is reduced by NADH/NADPH [2,3].…”