The Immobilization of Gossypol Derivative on N-Polyvinylpyrrolidone Increases its Water Solubility and Modifies Membrane-Active Properties

Abstract

The conjugate of the gossypol derivative megosin (1) with N-polyvinylpyrrolidone named rometin (2) was synthesized. The effects of 1 and 2 on the structure and permeability of human erythrocytes and rat liver mitochondria were compared. Compound 1 induced dose-dependent erythrocyte hemolysis and increased mitochondrial permeability, with concomitant changes in membrane structure as determined by ESR and fluorescence anisotropy methods. Immobilization of 1 on N-polyvinylpyrrolidone (compound 2) increased its water solubility and reduced the intensity of its effects on erythrocyte membrane integrity and mitochondrial permeability, which correlated with a decrease in the membranes structural changes induced by the compound. Although the same concentrations of free and N-polyvinylpyrrolidone bound 1 were used, far less (14)C-labeled 1 was incorporated into the membranes from complex than free 1. The increase in water solubility and the reduction of membrane-active properties of 1 after immobilization on N-polyvinylpyrrolidone could explain our previous observation of the decreased toxicity of 1.

Stabilization of erythrocytes against oxidative and hypotonic stress by tannins isolated from sumac leaves (Rhus typhina L.) and grape seeds (Vitis vinifera L.)

“…The factor G = I HV /I HH (grating correction factor) corrects the polarizing effects of the monochromator. The excitation wavelengths were 348 nm (DPH) and 340 nm (TMA-DPH) and the fluorescence emission was measured at 426 nm for DPH and 430 nm for TMA-DPH [27].…”

The interaction of PVP complexes of gossypol and its derivatives with an artificial membrane lipid matrix

“…This is probably what was observed in our DSC experiments. The details of the penetration of the gossypol molecule and its various derivatives into the hydrocarbon region of a lipid bilayer can be determined by interpreting ESR data [13,24]. If gossypol penetrated entirely into the lipid hydrocarbon region, its complicated structure should lead to a marked perturbation of the packing of the lipid molecules into the bilayer, excluding some of the lipid from cooperative melting.…”

Targeting Protein Neddylation to Inactivate Cullin-RING Ligases by Gossypol: A Lucky Hit or a New Start?

“…49 Several groups have synthesized a series of polyphenol derivatives of gossypol with similar or improved anti-cancer efficacy, 49,50 while the others have attempted to improve its solubility with a set of modifications. 51,52 None of these approaches, however, has significantly improved the efficacy of gossypol as an anticancer agent, nor for understanding its diversified mechanisms of action.…”