The immobilization of gossypol derivative on N-polyvinylpyrrolidone increases its water solubility and modifies membrane-active properties.
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.
Ionov
Maksim
M
Institute of Bioorganic Chemistry, Academy of Sciences, Tashkent, Uzbekistan.
Gordiyenko
Nataliya
N
Olchowik
Ewa
E
Baram
Nina
N
Zijaev
Khairulla
K
Salakhutdinov
Bakhtiyar
B
Bryszewska
Maria
M
Zamaraeva
Maria
M
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D006072:Gossypol / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D051336:Mitochondrial Membranes / Q000378:metabolism; D011205:Povidone / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013194:Staining and Labeling; D014867:Water / Q000737:chemistry*
D014867:Water; D011205:Povidone; D006072:Gossypol