The hemolytic activity of epoxydammarane triterpenoids.

The hemolytic activity of the epoxydammarane triterpenoids isolated from the Far-East species of the genus Betula and their semi-synthetic derivatives was investigated. Comparative studies of epoxydammarane triterpenoid activities at pH 5.5 and 5.0 and at 37 and 42 degrees C showed that 3-oxo, 3,11-dioxo, 3- and 11-acetoxy, as well as 3,11-diacetoxy derivatives had hemolytic potencies lower than the corresponding polyols; triterpenoids with a 3alpha-OH group were stronger than their analogues with a 3beta-OH group; epoxydammaranetriols were somewhat more potent than epoxydammaranediols. Triterpenoids esterified with malonic acid at C-3 possessed the strongest hemolytic activity among the tested compounds.

[Cytotoxic activity of dammarane triterpenoids from birch leaves]. / Tsitotoksicheskoe deistvie dammaranovykh triterpenoidov, vydelennykh iz list'ev berez.

Cytotoxic activity of dammarane triterpenoids isolated from beach leaves was studied. These substances differ from the native ginseng genin (20(S)-protopanaxadiol) by the number, location, or configuration of OH-groups. Using fertilized egg cells of sea urchin Stronglyocentrotus intermedius we demonstrate that the orientation of C-3 OH-group has no effect on cytotoxic activity of triterpenoids as well as a higher activity of a triterpenoid with 3 alpha,12 beta-OH as compared to a C-3 ketone but lower activity as compared to a triterpenoid with 3 alpha,17 alpha-OH. Depending on the number of OH-groups the cytotoxic activity of triterpenoids decreases in the row: tetraol > pentaol > triol. Dammar-24-ene-3 alpha 2 beta,17 alpha,20(S)-tetraol (compound IV) is cytotoxic for the Ehrlich ascite carcinoma cells and this effect is additive to cytotoxic activity of anthracycline antibiotic carminomycin in vitro. Compound IV changes the permeability and microviscosity of the tumor cell membranes.

New diterpenic altrosides of the fungus Acremonium striatisporum isolated from a sea cucumber.

Two new diterpenic glycosides, virescenosides M (1) and N (2), have been isolated from a marine strain of Acremonium striatisporum KMM 4401 associated with the holothurian Eupentacta fraudatrix. Their structures were determined on the basis of MS and NMR data as beta-D-altropyranosido-19-7-oxo-isopimara-8,15-diene-2alp ha, 3beta-diol (1) and beta-D-altropyranosido-19-isopimara-7, 15-diene-2alpha,3beta,6beta-triol (2). Three other altrosides (3-5), identified as virescenosides A, B, and C from the terrestrial strain Acremonium luzulae, were also isolated. The cytotoxic activity of the virescenosides was examined.

[A comparative study of the hemolytic activity of triterpene polyols of the dammarane series]. / Sravnitel'noe izuchenie gemoliticheskoi aktivnosti triterpenovykh poliolov dammaranovogo riada.

We studied membranotropic effect of dammarane-type triterpenes (isolated from birch leaves) with a variable side chain structure, as well as the number and configuration of OH groups as a function of temperature and pH. Polyols with an acyclic side chain and four OH groups proved to have a higher hemolytic activity as compared to polyols with three or five hydroxyl groups. The triterpenes, with tetrahydrofurane cycle as the side chain, exert a hemolytic effect at a more acidic pH (5.0) and higher temperature (45 degrees C), as compared to the polyols with acyclic side chain. Irrespective of the side chain structure, the compounds with a 24(S) configuration lysed the erythrocytes at lower rate, as compared to the compounds with a 24(R) configuration.

The membranotropic activity of cyclic acyldepsipeptides from bacterium Bacillus pumilus, associated with the marine sponge Ircinia sp.

The isolate of Bacillus pumilus associated with the marine sponge Ircinia sp. produced the surfactin-like lipopeptides, cyclic acyldepsipeptides. The hemolytic activity of individual cyclic acyldepsipeptides, bacircines (BI) 2, 3, 4, 5 and 5A having different acyl side chain structures (anteiso-C13, iso-C14, normal-C14, anteiso-C15, and iso-C15, respectively) was studied. The hemolytic power of bacircines depended on both the structure of the side chain (n->iso->anteiso-) and pH values (5.6 and 6.5 > 7.4). Hemolytic potency as a function of BI 5 concentration was given for pH 6.5; 7.4; 8.0; 9.0. pH dependent hemolysis induced by BI 5 was shown to be reversible. The membrane damaging potential of bacircine 5 (5 microM) at pH 6.5 was characterized by a higher rate of hemolysis and by a shorter time between the introduction of BI 5 solution into the RBC samples and the onset of hemolysis. Under this condition, BI 5 decreased abnormally the microviscosity of erythrocyte ghosts bilayer. The damaging potency of BI 5 decreased with an increase pH from 6.5 to 7.4 or its decrease from 6.5 to 4.9. It was shown that fatty acid bacircine fragment penetrated into the lipid bilayer to a depth of minimum 7 carbon atoms. Constants of dissociation of the Asp (pK 4.75) and Glu (pK 6.65) residues of bacircine in the lipid bilayer were obtained. These results showed that at pH 6.5 BI 5 possessed membranotropic activity in the monoionic form.

[The mechanism of the interaction of the pH-dependent cytostatic cauloside C with the membranes of tumor cells and liposomes]. / Mekhanizm vzaimodeistviia pH-zavisimogo tsitostatika kaulozida C s memranami opukholevykh kletok i liposom.

The effect of the medium pH on accumulation of [3H]-cauloside C by tumor cells, its intracellular localization, and interaction of the glicoside with membranes of tumor cells and liposomes has been studied. The shift towards weakly acids pH leads to the increase in the amount of cauloside C accumulated by tumor cells and changes the pattern of interaction of cauloside C with the membranes.

[Stimulation of nonspecific body resistance by mytilan, a polysaccharide isolated from the mussel. Crenomytilis grayanus]. / Stimuliatsiia nespetsificheskoi rezistentnosti organizma mitilanom--polisakharidom, vydelennym iz midii Crenomytilis grayanus.

The results of the study on the immunostimulant effect of mytilan, a polysaccharide isolated from Crenomytilus grayanus inhabiting the Sea of Japan are presented. It was shown that a single dose of the drug administered parenterally stimulated the natural protective reactions of the macroorganism evident from an increase in the leukocyte count in the peripheral blood of the experimental animals and the phagocytic activity of polymorphonuclear nuclear leukocytes. Mytilan stimulated humoral immunity. Its use brought about an increase in the hemolysin titers in response to administration of the sheep red blood cells card a significant increase in the number of antibody-forming cells as compared to the control. Mytiland had a preventive protective effect with regard to generalized pseudotuberculous and Salmonella infections. The drug increased the macroorganism resistance to both the psedotuberculous microbe and its toxins.