Benzophenanthridine Alkaloids Isolated fromEschscholtzia californicaCell Suspension Cultures Interact with Vasopressin (V₁) Receptors

Abstract

Chelerythrine and sanguinarine, two benzophenanthridine alkaloids, have been isolated from a crude methanolic extract of Eschscholtzia californica cell suspension cultures by successive fractionations. These two molecules exhibited affinity for rat liver vasopressin V1 receptors and are competitive inhibitors of [3H]-vasopressin binding within the micromolar range (Ki). Chelerythrine and sanguinarine represent two of the first non-peptidic structures providing original chemical leads for the design of synthetic vasopressin compounds.

Topoisomerase I Poisons and Suppressors as Anticancer Drugs

“…Cellular studies suggest that topoisomerase I is the major cytotoxic target for nitidine [114,117]. However, it is worth to bear in mind that benzophenanthridine alkaloids have been reported to mediate a variety of biological activity, including potent and selective inhibition of protein kinase C, binding to vasopressin V1 receptor, inhibition of taxol-mediated polymerization of tubulin and inhibition of cholinesterase systems, to cite only a few of them [118][119][120][121]. Therefore the antileukemic activity of nitidine may be due to the inhibition of topoisomerases and/or microtubule function.…”

Inhibitory Activity on Binding of Specific Ligands to the Human Angiotensin II AT1and Endothelin 1 ETAReceptors: Bioactive Benzo[c]phenanthridine Alkaloids from the Root ofBocconia frutescens

“…Benzo [c]phenanthridine alkaloids have a number of interesting pharmacological activities including antiviral [9], antitumoral [10], antimicrobial [11], antifungal [12] and anti-inflammatory properties [13]. They have also been shown to inhibit phosphorylation of proteins in the mitochondrial fraction of the rat heart [14]) and [ 3 H]-vasopressin binding [15]. They may also interact with biopolymers by mean of their reactive iminium group and intercalating in this way DNA [16].…”

Sanguinarine

“…Arginine vasopressin (AVP) interacts with three subtypes of vasopressin receptors, V 1 , V 2 , and V 3 , mediating vasoconstriction, water reabsorption, and central nervous system effects, respectively (Treschan and Peters 2006). In 1992, Granger et al showed that SA isolated from Eschscholtzia californica ; competitively inhibited binding of AVP to V 1 receptors (Granger et al 1992). In rat liver plasma membranes SA competed dose‐dependently for binding to V 1 receptors with an IC 50 of 2.6 × 10 −5 M. The IC 50 was determined by the inhibition of agonist, [ 3 H]AVP‐specific binding using increasing concentrations of SA.…”