Irina G. Agafonova

Hemolytic activities of triterpene glycosides from the holothurian order dendrochirotida: Some trends in the evolution of this group of toxins

Hemolysis and K+ loss from mouse erythrocytes, induced by triterpene glycosides and their derivatives from this order of sea cucumbers were studied. Sulfate groups, attached to position 4 of the first xylose residue and to position 6 of the third glucose residue of the branched pentaosides, having 3-O-methyl-groups in terminal monosaccharide moieties increase K+ loss. A sulfate group at C-4 of the first xylose residue increases the hemolytic activity while a sulfate at C-6 of the third monosaccharide unit decreases it. A sulfate group at C-6 of terminal 3-O-methylglucose drastically decreases the hemolytic activity and rate of K+ loss. The presence of a sulfate group at the first xylose residue in glycosides having no 3-O-methyl group at the terminal monosaccharide decreases hemolytic activity and rate of K+ loss. The presence of the 16-ketone group in aglycones having the 7(8)-double bond significantly decreases activity. These results correlate with the previously proposed trends in evolution of sea cucumber glycosides from substances having sulfate groups at C-6 of glucose and 3-O-methylglucose units to substances sulfated at C-4 of the first xylose or having no sulfate groups, and from substances with aglycone 16-ketone to substances having no oxygen functions in this position.

Antitumor activity of the immunomodulatory lead Cumaside

A new immunomodulatory lead Cumaside that is a complex of monosulfated triterpene glycosides from the sea cucumber Cucumaria japonica and cholesterol possesses significantly less cytotoxic activity against sea urchin embryos and Ehrlich carcinoma cells than the corresponding glycosides. Nevertheless Cumaside has an antitumor activity against different forms of experimental mouse Ehrlich carcinoma in vivo both independently and in combination with cytostatics. The highest effect occurs at a treatment once a day for 7 days before the tumor inoculation followed by Cumaside treatment once a day for 7 days. Prophylactic treatment with Cumaside and subsequent therapeutic application of 5-fluorouracil suppressed the tumor growth by 43%.

Effect of Histochrome on Brain Vessels and Research and Exploratory Activity of Senescence-Accelerated OXYS Rats

Changes in the diameter of brain vessels and intensity of collateral blood flow typical of chronic ischemia were detected by magnetic resonance imaging in senescence-accelerated OXYS rats demonstrating reduced (compared to Wistar rats) research and exploratory activity. Histochrome (antioxidant drug) produced positive effects on cerebral vessels in OXYS rats by stimulating collateral blood flow and acting as a vasodilator agent. Analysis of correlations showed that these effects of histochrome were closely related to its capacity to activate research and exploratory activity and reduce anxiety of OXYS rats in the open field test.

Evaluation of Effects of Histochrome and Mexidol on Structural and Functional Characteristics of the Brain in Senescence-Accelerated OXYS Rats by Magnetic Resonance Imaging

The effects of histochrome and mexidol on the morphology and function of the brain and behavior were studied in senescence-accelerated OXYS and Wistar rats. MRI showed that signs of neurodegenerative changes were present in OXYS rats at the age of 3 months and were pronounced at the age of 12 months. Histochrome (1 mg/kg, 5 days) more effectively than mexidol (4 mg/kg, 7 days) reduced anxiety and increased exploratory activity of 1-yearold OXYS rats. Both drugs improved the morphology and function of the brain. Their effects consisting in correction of diffuse changes in the white matter and reduction of edema were comparable; in addition, histochrome reduced the intensity of demyelinization processes.

Steroidal Triglycosides, Kurilensosides A, B, and C, and Other Polar Steroids from the Far Eastern Starfish Hippasteria kurilensis

Three novel steroidal triglycosides, designated as kurilensosides A, B, and C (1- 3), were isolated along with a new steroidal diglycoside, kurilensoside D (4), and two new (6, 7) and one known (5) polyhydroxysteroid from the alcoholic extract of the Far Eastern starfish Hippasteria kurilensis. Compounds 1-3 are the first triglycosides containing two carbohydrate chains found from starfish. The structures of 1-7 were elucidated by spectroscopic methods (mainly 2D NMR) and chemical derivatization. Glycosides 1-4 and steroids 6 and 7 inhibited sea urchin egg fertilization by sperm preincubated with these compounds.

Sulfated steroid glycosides from the Viet Namese starfish Linckia laevigata

Five sulfated steriodal compounds including one new glycoside called linckoside L7 (1) and four previously known glycosides 2–5 were isolated from the starfish Linckia laevigata. The structure sodium (22E, 24R)-3-O-(2-O-methyl-β-D-xylopyranosyl)-29-O-(β-D-xylopyranosyl)-24-ethylcholest-4,22-dien-3β,6β,8,15α,16β,29-hexaol 15-O-sulfate was proposed for L7. Linckoside L7 inhibited fertilization and egg-cell development in the sea urchin Strongylocentrotus intermedius.

Endothelial dysfunction of cerebral and major arteries during chronic obstructive disease.

Vasomotor activity of the major and cerebral arteries was studied in mice with chronic obstructive pulmonary disease. Regional differences were revealed in the endothelium-dependent response of arteries. The development of chronic obstructive pulmonary disease was associated with a paradoxical response of the dilatational component of vasoregulation against the background of increased constrictive influences of the vascular endothelium in the major and cerebral vessels.

Highly hydroxylated steroids of the starfish Archaster typicus from the Vietnamese waters

Five new steroidal compounds, including an unusual glucoside, along with several known steroids were isolated from the starfish Archaster typicus collected in shallow waters of Quang Ninh province (Vietnam). Three new compounds are 27-nor-cholestane derivatives and the other two are 24,26-dihydroxycholestane derivatives. A biogenesis pathway for the unusual side chain of 27-nor-cholestane derivatives is proposed. Isolated compounds presented moderate toxic effects in the sperm- and 8-blastomere tests on embryonal development of the sea urchin Strongylocentrotusintermedius.

Polar steroidal compounds from the Far-Eastern starfish Lethasterias nanimensis chelifera

In addition to the salts described previously (with a sulfated steroid as the anion and the alkaloid salsolinol as the cation), nine other steroidal compounds including three new compounds were isolated from the Far-Eastern starfish Lethasterias nanimensis chelifera collected near the coast of the Onekotan island (Kuril isles). A nonsteroidal compound found in this starfish is (1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid. The structures of the isolated compounds were determined by NMR spectroscopy and mass spectrometry.

Biological activity of disulfated polyhydroxysteroids from the pacific brittle star Ophiopholis aculeata

The action of (20R)-cholesta-5,25-diene-3 alpha, 4 beta, 21-triol 3,21-disulfate and its 25,26-dihydroanalog from the Pacific brittle star Ophiopholis aculeata was studied on mouse cancer cells, lymphocytes and erythrocytes. The cytotoxic and hemolytic effects were not observed for both steroids at the wide range of concentrations. Both steroids inhibited 3H-Thymidine (but not 3H-Uridine) incorporation into Ehrlich carcinoma cells. It was the first time shown that some sulfated marine polyhydroxylated steroids stimulate the influx of Ca2+ into cells. (20R)-Cholesta-5,25-diene-3 alpha, 4 beta, 21-triol 3,21-disulfate was two times more active than its 25,26-dihydro-analog.