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The objective of this study is analysis of stability and antioxidant and antiradical activities of the gossypol derivative - megosin conjugated with N-polyvinylpyrrolidone (PVP). The results of study have shown the greater stability of megosin+PVP than megosin in aqueous solution of wide range of pH. Here we also demonstrated that megosin+PVP, named rometin, possess high antioxidant activity in the same range as well known antioxidant trolox as determined by its ability to scavenge free ABTS(+) and DPPH radicals in vitro. In addition, megosin+PVP was able to prevent accumulation of products of lipid peroxidation (thiobarbituric acid reactive substances and diene conjugates) and lysophospholipids formation in mitochondria membranes caused by CCl(4)-induced oxidative stress in rat liver in vivo. Furthermore, megosin+PVP rescued mitochondrial functions, such as respiration and oxidative phosphorylation, which declined after CCl(4) administration. Thus we present that the conjugation of megosin to PVP increase its stability and remain antioxidant activity in vivo and in vitro.

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.

Azo-coupling of diazotized aromatic amines with gossypol and gossypolimines was studied. The physicochemical properties and interferon-inducing activity of the products were determined. It was found that the interferon-inducing activity depended on the reaction type, the position of functional groups (o-, m-, p-) in the added substituents, and the dose and contact time of the compounds with the cells.

New azo-derivatives of gossypol and its imines were described. Their physicochemical properties and data on their interferon-inducing activity were presented.

New azo derivatives of gossypol are described. Their physicochemical properties are reported. The presence of hydroxyazo- and quinonhydrazo-tautomers is proposed.

The results are given of a study of the hydrolysis of alkyl- and heterylimines of gossypol at various pH values.

The results are given of a study of gossypol, its physiologically active derivatives, and their complexes with N-polyvinylpyrrolidone (M.m. 8000) in various media. It has been shown that the production of complexes permits the creation not only of water-soluble forms but also of more stable forms of the compounds.

The method of obtaining radioactively labeled14C-gossypol-acetic acid has been improved: from it have been synthesized14C-derivatives of gossypol and their complexes with N-polyvinylpyrrolidone. A comparative study has been made of the pharmacokinetics of batriden, megosin, and their water-soluble complexes.

It has beeen shown that water-soluble complexes of gossypol derivatives obtained by their immobilization on polyvinylpyrrolidone posses a lower membrane activity than the initial substances. The degree of interaction of the substances under investigation with biomembranes has been determined from the change in the intensity of the flourescence of I-anilinonaphthalene-8-sulfonic acid (ANS).

Information is given on the antiviral and interferon-inducing activities of gossypol and its derivatives.

This review of the literature and of the authors' own investigations is devoted to the biological activity of gossypol and its derivatives. Certain results of the structural—functional analysis of gossypol ethers and the products of its condensation with amines and CH-acids are discussed. The results of pharmacokinetic investigations of radioactively labeled samples of gossypol and its physiologically active derivatives are given.

In this paper, we present the results of a study on the membrane-active properties of gossypol, its derivatives and their polyvinylpyrrolidone complexes as assessed by differential scanning calorimetry and by the fluorescent probe method. The latter revealed the change in polarization of the incident radiation caused by the action of the polyphenol on the artificial membrane lipid matrix.

Imines of methyl ethers of gossypol have been synthesized for the first time, their structures have been shown, and their immunomodulating activities have been determined. The quinoid form of existence of the imines of the dimethyl ether and the benzoid form of the imine of the mexamethyl ether of gossypol have been shown.

Samples of batriden (a drug based on gossypol) radioactively labeled with14C in different parts of the molecule have been synthesized. Pharmacokinetic investigations of the14C-batridens have enabled the mechanism of the action of the drug to be elucidated.

Information is given on new gossypol imines. The use of hydrazines as the imine components produces Schiff bases of gossypol existing in the benzoid form.

The results are given of a comparative spectroscopic study of some gossypol derivatives and their complexes with N-polyvinylpyrrolidone.

The pharmacokinetics of PHL-6 and interferon synthesis dynamic in the target organs (tissues) of mice were studied during its and intraperitoneal administration. In the experimental setting, there was a direct correlation between the interferon production in the murine organs with single PHL-6 and distribution of 14C PHL-6. The highest radioactivity with its oral administration was detected in the liver and intestine. Interferon was actively synthesized in the intestine, liver and serum, showing the levels of 20000, 1024-2048 and 512-1024 IU/ml, respectively. The prolonged action of the drug was in good agreement with the low PHL-6 excretion from the body. It was also shown that almost the whole radiation dose 1 (greater than 98%) was excreted with feces and urine after single and chronic administrations of uniformly labeled PHL-6 which proved important clinical drug use.

In continuation of our search for physiologically active compounds among aromatic aldehyde derivatives, we synthesized the sodium salts of some arylideniminoethane sulfonic acids. Certain hydroxyalkyloxybenzaldehydes and naphthaldehydes were used for condensation with sodium B-aminoethyl sulfate. The resultant compounds are water-soluble brightly colored powderlike substances with poor solubility in organic solvents (Table i).

It has been shown on the basis of the results of a study of PMR spectra that, regardless of its source and method of purification, in weakly polar solvents gossypol exists predominantly in the aldehyde form.

1. By direct analysis of daughter ions, a study has been made of the paths of fragmentation of the molecular and fragment ions manifested in the mass spectra of arylidene derivatives of barbituric acid and 2-thioxy-4-thiazolidone. It has been shown that the fragmentation of these compounds proceeds through decomposition of the heterocyclic part and the substituents of the aryl part of the molecule. 2. It has been shown that the condensation of barbituric acid and 2-thioxy-4-thiazolidone with o-hydroxyaryl aldehydes proceeds with the formation of anomalous products, the structure of which has been established from an analysis of the spectral data.

Information is given on the immunosuppressive activity of a number of gossypol derivatives, and it is shown that practically all the compounds studied are immunotropic. The structural-functional relationship and the dose-dependent nature of the action of the substances obtained are shown.

A number of new Schiff's bases of gossypol with aromatic amines and sulfanilamide compounds has been obtained. It has been shown by UV and PMR spectroscopy and x-ray structural analysis that in some solvents they exist predominantly in the quinoid form. For dianilinegossypol (in the solid state) the quinoid structure has been demonstrated and two polymorphic modifications have been revealed by x-ray structural analysis.

1. The existence of a tautomeric equilibrium between the aldehyde and lactol forms gossypol has, for the first time, been demonstrated through NMR spectroscopy. In DMSO, gossypol exists primarily in the lactol form, and primarily in the aldehyde form in acids, bases, and inert solvents. 2. The method of preparation of the ethers of this compound determines the form of the product obtained.

The 5-arylidenebarbituric acids were obtained by a known method [i] and were colored substances, poorly soluble in normal organic solvents (see Table i). UV spectra for the 5arylidenebarbituric acids have, in addition to characteristic absorption for them in the range 245-255 nm, intensive absorption at 380-420 nm. A bathochromic shift to longer wave lengths in observed on increasing the conjugation chain through the aldehyde component.

The clastogenic and mutagenic activities of a new antifertility and antitumor agent gossypol were studied in the mouse male germ cells. Results of the present work indicate that at the doses 125 and 250 mg/kg the drug does not significantly increase frequencies of the micronuclei in the early spermatids and sperm head abnormalities. Hence, genotoxic influence can not be proposed as responsible for the antifertility effect of gossypol.

This review summarizes the main results of experimental and clinical studies of a new antifertile agent, gossypol, a polyphenolic compound isolated from the cotton. This compound disturb the normal course of spermatogenesis and affects, first of all, the locomotory system of mature spermatozoa of the man and some mammal species. The mechanism of gossypol action on the development of germ cells is discussed. Since the action of gossypol is reversible and it does not induce strong side effects, the possibility of its application for the control of birth rate is considered.