New Triterpene Glycosides from the Far Eastern Starfish Solaster pacificus and Their Biological Activity

Malyarenko, Timofey V.; Kicha, A. A.; Kalinovsky, Anatoly I.; Dmitrenok, Pavel S.; Malyarenko, Olesya S.; Kuzmich, Alexandra S.; Stonik, Valentin A.; Ivanchina, Natalia V.

doi:10.3390/biom11030427

Cited by 13 publications

(35 citation statements)

References 33 publications

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“…In the series of magnumosides B 1 (8) and C 1 (12) and magnumosides A 2 (5), B 2 (9), C 2 (13), with the hydroxyl group in the aglycone side chains, the disulfated tetraosides 12 and 13 were the most active compounds, while in the series of magnumosides A 3 (6), B 3 (10), C 3 (14) and magnumosides A 4 (7), B 4 (11), C 4 (15), which comprised the side chains with a double bond, the monosulfated tetraosides 10 and 11 showed the strongest effect (Table 1). Magnumosides of group A (5-7) demonstrated considerable hemolytic effects despite the absence of a tetrasaccharide linear fragment (Table 1).…”

Section: The Dependence Of the Glycosides Hemolytic Activity On Their Carbohydrate Chain Structurementioning

confidence: 99%

“…This complexing reaction of both the animal and plant saponins leads to the formation of pores, the permeabilization of cells, and in the case of red blood cells for which the membranes are known to be enriched in cholesterol [10], the subsequent loss of hemoglobin in the extracellular medium [11]. Malyarenko et al tested a series of triterpene glycosides isolated from the starfish Solaster pacificus that had exogenic origin from a sea cucumber eaten by this starfish [12]. The authors showed that the addition of cholesterol to corresponding tumor cell culture media significantly decreases the cytotoxicity of these glycosides.…”

Section: Introductionmentioning

confidence: 99%

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Structure-Activity Relationships of Holothuroid’s Triterpene Glycosides and Some In Silico Insights Obtained by Molecular Dynamics Study on the Mechanisms of Their Membranolytic Action

et al. 2021

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The article describes the structure-activity relationships (SAR) for a broad series of sea cucumber glycosides on different tumor cell lines and erythrocytes, and an in silico modulation of the interaction of selected glycosides from the sea cucumber Eupentacta fraudatrix with model erythrocyte membranes using full-atom molecular dynamics (MD) simulations. The in silico approach revealed that the glycosides bound to the membrane surface mainly through hydrophobic interactions and hydrogen bonds. The mode of such interactions depends on the aglycone structure, including the side chain structural peculiarities, and varies to a great extent. Two different mechanisms of glycoside/membrane interactions were discovered. The first one was realized through the pore formation (by cucumariosides A1 (40) and A8 (44)), preceded by bonding of the glycosides with membrane sphingomyelin, phospholipids, and cholesterol. Noncovalent intermolecular interactions inside multimolecular membrane complexes and their stoichiometry differed for 40 and 44. The second mechanism was realized by cucumarioside A2 (59) through the formation of phospholipid and cholesterol clusters in the outer and inner membrane leaflets, correspondingly. Noticeably, the glycoside/phospholipid interactions were more favorable compared to the glycoside/cholesterol interactions, but the glycoside possessed an agglomerating action towards the cholesterol molecules from the inner membrane leaflet. In silico simulations of the interactions of cucumarioside A7 (45) with model membrane demonstrated only slight interactions with phospholipid polar heads and the absence of glycoside/cholesterol interactions. This fact correlated well with very low experimental hemolytic activity of this substance. The observed peculiarities of membranotropic action are in good agreement with the corresponding experimental data on hemolytic activity of the investigated compounds in vitro.

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Section: The Dependence Of the Glycosides Hemolytic Activity On Their Carbohydrate Chain Structurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structure-Activity Relationships of Holothuroid’s Triterpene Glycosides and Some In Silico Insights Obtained by Molecular Dynamics Study on the Mechanisms of Their Membranolytic Action

et al. 2021

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“…The key HMBC correlations H 3 -21/C-17, C-20, C-22 and H-22/C-17, C-21 and ROESY correlations H 3 -21/H-16, H-17, H-22, and H 2 -22/H-16 supported the total structure of the side chain ( Figure 1 , Figures S61 and S62 ). The NMR spectroscopic data of the aglycon part of 7 were coincident with those of the known cucumarioside A 10 from E. fraudatrix and pacificusoside B from S. pacificus with 23,24,25,26,27-pentanor-lanosta-7,20(22)-diene-18(16)-lactone-3β-ol aglycon [ 28 , 33 ].…”

Section: Resultsmentioning

confidence: 76%

“…In addition, very recently, we reported about the isolation and structure elucidation of three new triterpene glycosides, pacificusosides A–C, and three previously known triterpene glycosides, cucumariosides C 1 , C 2 , and A 10 , from the Far Eastern starfish Solaster pacificus . We supposed that these compounds were obtained with diet from sea cucumbers belonging to the genus Eupentacta and partly metabolized in the starfish [ 28 ]. We have also described the cytotoxicity of isolated triterpene glycosides against human embryonic kidney HEK 293 cells, colorectal carcinoma HT-29 cells, melanoma RPMI-7951 cells, and breast cancer MDA-MB-231 cells using MTS assay.…”

Section: Introductionmentioning

confidence: 99%

“…At the same time, the cytotoxic effects of the investigated triterpene glycosides were reduced by cholesterol, such as with the similar effects of the previously investigated triterpene glycosides. Finally, pacificusoside C and cucumariosides C 1 and C 2 almost completely suppressed the colony formation of the HT-29, RPMI-7951, and MDA-MB-231 cells at a non-toxic concentration of 0.5 μM [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Anticancer and Cancer-Preventive Activity of New Triterpene Glycosides from the Far Eastern Starfish Solaster pacificus

Malyarenko

Kicha

et al. 2022

Marine Drugs

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Sea stars or starfish (class Asteroidea) and holothurians or sea cucumbers (class Holothuroidea), belonging to the phylum Echinodermata (echinoderms), are characterized by different sets of glycosidic metabolites: the steroid type in starfish and the triterpene type in holothurians. However, herein we report the isolation of eight new triterpene glycosides, pacificusosides D–K (1–3, 5–9) along with the known cucumarioside D (4), from the alcoholic extract of the Far Eastern starfish Solaster pacificus. The isolated new compounds are closely related to the metabolites of sea cucumbers, and their structures of 1–3 and 5–9 were determined by extensive NMR and ESIMS techniques. Compounds 2, 5, and 8 have a new type of tetrasaccharide chain with a terminal non-methylated monosaccharide unit. Compounds 3, 6, and 9 contain another new type of tetrasaccharide chain, having 6-O-SO3-Glc as one of the sugar units. The cytotoxic activity of 1–9 against non-cancerous mouse epidermal cells JB6 Cl41 and human melanoma cell lines SK-MEL-2, SK-MEL-28, and RPMI-7951 was determined by MTS assay. Compounds 1, 3, 4, 6, and 9 showed potent cytotoxicity against these cell lines, but the cancer selectivity (SI > 9) was observed only against the SK-MEL-2 cell line. Compounds 1, 3, 4, 6, and 9 at the non-toxic concentration of 0.1 μM significantly inhibited neoplastic cell transformation of JB6 Cl41 cells induced by chemical carcinogens (EGF, TPA) or ionizing radiation (X-rays and UVB). Moreover, compounds 1 and 4 at the non-toxic concentration of 0.1 µM possessed the highest inhibiting activity on colony formation among the investigated compounds and decreased the colonies number of SK-MEL-2 cells by 64% and 70%, respectively. Thus, triterpene glycosides 1 and 4 can be considered as prospective cancer-preventive and anticancer-compound leaders.

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Total Synthesis of Starfish Cyclic Steroid Glycosides

Zhu

Geng

2022

Angewandte Chemie

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Starfishes have evolved with a special type of secondary metabolites, namely starfish saponins, to ward off various predators and parasites; among them, the starfish cyclic steroid glycosides stand out structurally, featuring a unique 16-membered ring formed by bridging the steroidal C3 and C6 with a trisaccharide. The rigid cyclic scaffold and the congested and vulnerable steroid-sugar etherate linkage present an unprecedented synthetic challenge. Here we report a collective total synthesis of the major starfish cyclic steroid glycosides, namely luzonicosides A (1) and D (2) and sepositoside A (3), with an innovative approach, which entails a de novo construction of the ether-linked hexopyranosyl units, use of olefinic pyranoses as sugar precursors, and a decisive ring-closing glycosylation under the mild gold(I)-catalyzed conditions.

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New Triterpene Glycosides from the Far Eastern Starfish Solaster pacificus and Their Biological Activity

Cited by 13 publications

References 33 publications

Structure-Activity Relationships of Holothuroid’s Triterpene Glycosides and Some In Silico Insights Obtained by Molecular Dynamics Study on the Mechanisms of Their Membranolytic Action

Structure-Activity Relationships of Holothuroid’s Triterpene Glycosides and Some In Silico Insights Obtained by Molecular Dynamics Study on the Mechanisms of Their Membranolytic Action

In Vitro Anticancer and Cancer-Preventive Activity of New Triterpene Glycosides from the Far Eastern Starfish Solaster pacificus

Total Synthesis of Starfish Cyclic Steroid Glycosides

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