Triterpene Glycosides from the Far Eastern Sea Cucumber Psolus chitonoides: Chemical Structures and Cytotoxicities of Chitonoidosides E1, F, G, and H

Four new triterpene disulfated glycosides, chitonoidosides E1 (1), F (2), G (3), and H (4), were isolated from the Far-Eastern sea cucumber Psolus chitonoides and collected near Bering Island (Commander Islands) at depths of 100–150 m. Among them there are two hexaosides (1 and 3), differing from each other by the terminal (sixth) sugar residue, one pentaoside (4) and one tetraoside (2), characterized by a glycoside architecture of oligosaccharide chains with shortened bottom semi-chains, which is uncommon for sea cucumbers. Some additional distinctive structural features inherent in 1–4 were also found: the aglycone of a recently discovered new type, with 18(20)-ether bond and lacking a lactone in chitonoidoside G (3), glycoside 3-O-methylxylose residue in chitonoidoside E1 (1), which is rarely detected in sea cucumbers, and sulfated by uncommon position 4 terminal 3-O-methylglucose in chitonoidosides F (2) and H (4). The hemolytic activities of compounds 1–4 and chitonoidoside E against human erythrocytes and their cytotoxic action against the human cancer cell lines, adenocarcinoma HeLa, colorectal adenocarcinoma DLD-1, and monocytes THP-1, were studied. The glycoside with hexasaccharide chains (1, 3 and chitonoidoside E) were the most active against erythrocytes. A similar tendency was observed for the cytotoxicity against adenocarcinoma HeLa cells, but the demonstrated effects were moderate. The monocyte THP-1 cell line and erythrocytes were comparably sensitive to the action of the glycosides, but the activity of chitonoidosides E and E1 (1) significantly differed from that of 3 in relation to THP-1 cells. A tetraoside with a shortened bottom semi-chain, chitonoidoside F (2), displayed the weakest membranolytic effect in the series.

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Unusual Structures and Cytotoxicities of Chitonoidosides A, A1, B, C, D, and E, Six Triterpene Glycosides from the Far Eastern Sea Cucumber Psolus chitonoides

Marine Drugs ◽

10.3390/md19080449 ◽

2021 ◽

Vol 19 (8) ◽

pp. 449

Author(s):

Alexandra S. Silchenko ◽

Anatoly I. Kalinovsky ◽

Sergey A. Avilov ◽

Pelageya V. Andrijaschenko ◽

Roman S. Popov ◽

...

Keyword(s):

Sea Cucumber ◽

Human Cancer ◽

Carbohydrate Chain ◽

Cytotoxic Activities ◽

Unexpected Finding ◽

Commander Islands ◽

Sugar Chain ◽

Human Cancer Cell Lines ◽

Far Eastern ◽

Bering Island

Six new triterpene tetra-, penta- and hexaosides, chitonoidosides A (1), A1 (2), B (3), C (4), D (5), and E (6), containing one or two sulfate groups, have been isolated from the Far-Eastern sea cucumber Psolus chitonoides, collected near Bering Island (Commander Islands) from the depth of 100–150 m. Three of the isolated compounds (1, 3 and 6) are characterized by the unusual aglycone of new type having 18(20)-ether bond and lacking a lactone in contrast with wide spread holostane derivatives. Another unexpected finding is 3-O-methylxylose residue as a terminal unit in the carbohydrate chains of chitonoidosides B (3), C (4), and E (6), which has never been found before in the glycosides from holothurians belonging to the Psolidae family. Moreover, this monosaccharide is sulfated in the compound 4 into unprecedented 3-O-methylxylose 4-O-sulfate residue. Chitonoidoside C (4) is characterized by tetrasaccharide moiety lacking a part of the bottom semi-chain, but having disaccharide fragment attached to C-4 of Xyl1. Such architecture is not common in sea cucumber glycosides. Cytotoxic activities of the compounds 1–5 against mouse and human erythrocytes and human cancer cell lines: adenocarcinoma HeLa, colorectal adenocarcinoma DLD-1, and leukemia promyeloblast HL-60 cells were studied. The cytotoxic effect of chitonoidoside d (5) was the most significant in this series due to the presence of pentasaccharide disulfated sugar chain in combination with holostane aglycone. Surprisingly, the glycosides 1 and 3, comprising the new aglycone without γ-lactone, demonstrated similar activity to the known compounds with holostane aglycones. Chitonoidoside C (4) was less cytotoxic due to the different architecture of the carbohydrate chain compared to the other glycosides and probably due to the presence of a sulfate group at C-4 in 3-O-MeXyl4.

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Cucumarioside E from the Far Eastern Sea Cucumber Cucumaria japonica (Cucumariidae, Dendrochirotida), New Minor Monosulfated Holostane Triterpene Pentaoside with Glucose as the Second Monosaccharide Residue

Natural Product Communications ◽

10.1177/1934578x1501000621 ◽

2015 ◽

Vol 10 (6) ◽

pp. 1934578X1501000 ◽

Cited By ~ 2

Author(s):

Alexandra S. Silchenko ◽

Anatoly I. Kalinovsky ◽

Pavel S. Dmitrenok ◽

Vladimir I. Kalinin ◽

Andrey N. Mazeika ◽

...

Keyword(s):

Mass Spectrometry ◽

Structural Feature ◽

Sea Cucumber ◽

2D Nmr ◽

Monosaccharide Residue ◽

Sea Cucumbers ◽

Unique Structural Feature ◽

Far Eastern ◽

Cucumaria Japonica ◽

Carbohydrate Chains

New minor triterpene glycoside, cucumarioside E (1) has been isolated from the Far Eastern sea cucumber Cucumaria japonica. The structure of the glycoside was elucidated by 2D-NMR specroscopy and mass-spectrometry. The glycoside has glucose instead of quinovose as the second monosaccharide residue and xylose as third monosaccharide residue that is unique structural feature for triterpene glycosides carbohydrate chains from sea cucumbers belonging to the genus Cucumaria.

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Cytotoxic Polyketides from the Marine Sponge-Derived Fungus Pestalotiopsis heterocornis XWS03F09

Molecules ◽

10.3390/molecules24142655 ◽

2019 ◽

Vol 24 (14) ◽

pp. 2655 ◽

Cited By ~ 2

Author(s):

Lei ◽

Zhou ◽

Hu ◽

Niu ◽

...

Keyword(s):

Marine Sponge ◽

Spectroscopic Analysis ◽

Fermentation Broth ◽

Human Cancer ◽

Optical Rotation ◽

Cytotoxic Activities ◽

Human Cancer Cell Lines ◽

Chemical Structures ◽

Ic50 Values ◽

New Compounds

Four new compounds, including two new polyketides, heterocornols M and N (1, 2), and a pair of epimers, heterocornols O and P (3, 4), were isolated from the fermentation broth of the marine sponge-derived fungus Pestalotiopsis heterocornis XWS03F09, together with three known compounds (5–7). The new chemical structures were established on the basis of a spectroscopic analysis, optical rotation, experimental and calculated electronic circular dichroism (ECD). All of the compounds (1–7) were evaluated for their cytotoxic activities, and heterocornols M-P (1–4) exhibited cytotoxicities against four human cancer cell lines with IC50 values of 20.4–94.2 μM.

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Bioactive Components of Fissistigma cupreonitens

Natural Product Communications ◽

10.1177/1934578x1801300607 ◽

2018 ◽

Vol 13 (6) ◽

pp. 1934578X1801300 ◽

Cited By ~ 1

Author(s):

I-Hsiao Chen ◽

Ming-Yi Yang ◽

Shin-Hun Juang ◽

Chia-Lin Lee ◽

Tran-Dinh Thang ◽

...

Keyword(s):

Cell Line ◽

Human Cancer ◽

Spectroscopic Methods ◽

Human Cancer Cell ◽

Bioactive Components ◽

Standard Drug ◽

Human Cancer Cell Lines ◽

Chemical Structures ◽

Phytochemical Investigation ◽

First Time

Phytochemical investigation of Fissistigma cupreonitens (Annonaceae) led to the isolation of 34 compounds. The chemical structures of all compounds were determined by spectroscopic methods. Among the isolates, compounds 20–27 and 31–34 were reported from this genus for the first time. From the results of the cytotoxicity assay against three human cancer cell lines (NCI-H226, NPC-TW01, and Jurkat E6–1), oxoaporphine compounds oxoxylopine (1), oxocrebanine (3), kuafumine (4) and lysicamine (5), and the flavonoid adunctin E (26) displayed significant cytotoxicity against NCI-H226 cell line, with IC50 values of 8.45, 8.10, 8.54, 12.83 and 12.00 μM, respectively, in comparison with the standard drug, cisplatin with IC50 of 13.37 μM.

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COMPARE Analysis, a Bioinformatic Approach to Accelerate Drug Repurposing against Covid-19 and Other Emerging Epidemics

SLAS DISCOVERY Advancing Life Sciences ◽

10.1177/2472555220975672 ◽

2020 ◽

pp. 247255522097567

Author(s):

Imad Naasani

Keyword(s):

Human Cancer ◽

Drug Repurposing ◽

Data Repository ◽

Human Cancer Cell Lines ◽

Chemical Structures ◽

Drug Molecules ◽

Growth Inhibitory ◽

Antiviral Activities ◽

Bioinformatic Approach ◽

Compare Analysis

A novel bioinformatic approach for drug repurposing against emerging viral epidemics like Covid-19 is described. It exploits the COMPARE algorithm, a public program from the National Cancer Institute (NCI) to sort drugs according to their patterns of growth inhibitory profiles from a diverse panel of human cancer cell lines. The data repository of the NCI includes the growth inhibitory patterns of more than 55,000 molecules. When candidate drug molecules with ostensible anti-SARS-CoV-2 activities were used as seeds (e.g., hydroxychloroquine, ritonavir, and dexamethasone) in COMPARE, the analysis uncovered several molecules with fingerprints similar to the seeded drugs. Interestingly, despite the fact that the uncovered drugs were from various pharmacological classes (antiarrhythmic, nucleosides, antipsychotic, alkaloids, antibiotics, and vitamins), they were all reportedly known from published literature to exert antiviral activities via different modes, confirming that COMPARE analysis is efficient for predicting antiviral activities of drugs from various pharmacological classes. Noticeably, several of the uncovered drugs can be readily tested, like didanosine, methotrexate, vitamin A, nicotinamide, valproic acid, uridine, and flucloxacillin. Unlike pure in silico methods, this approach is biologically more relevant and able to pharmacologically correlate compounds regardless of their chemical structures. This is an untapped resource, reliable and readily exploitable for drug repurposing against current and future viral outbreaks.

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Strategies To Identify Effective Treatments For Proteasome Inhibitor Resistant Multiple Myeloma

Blood ◽

10.1182/blood.v122.21.278.278 ◽

2013 ◽

Vol 122 (21) ◽

pp. 278-278

Author(s):

Brian Van Ness ◽

Holly A. F. Stessman ◽

Linda B. Baughn ◽

Aatif Mansoor ◽

Amit Mitra ◽

...

Keyword(s):

Data Base ◽

Cell Lines ◽

Research Funding ◽

Human Cancer ◽

Expression Profiles ◽

Single Agent ◽

Cross Resistance ◽

Human Cancer Cell Lines ◽

Chemical Structures

Abstract Despite the introduction of effective new agents in the treatment of myeloma, the disease is still mostly incurable. Among the most significant issues is the heterogeneity of the disease, with accumulation of multiple genetic abnormalities among patients, resulting in disease refractory to some highly active agents, or the emergence of resistance leading to aggressive relapse. We have focused efforts on modeling drug sensitivity, and generating both genetic and biomarker signatures of response and resistance to the proteasome inhibitors (PIs): bortezomib (Btz), MLN2238 (Takeda) and carfilzomob (Onyx). Using mouse and human myeloma cell lines we dose escalated with bortezomib and selected bortezomib-resistant (Btz-R) lines (that showed cross resistance to MLN2238 and carfilzomib). We previously reported the identification of gene expression signatures that distinguish sensitivity or resistance to bortezomib (Stessman, et al., Mol Cancer Ther 12:1140, 2013). We then took three approaches to identify effective strategies to treat bortezomib resistance: 1) The connectivity map (CMAP) data base contains treatment induced transcriptional signatures from over 1300 bioactive compounds in human cancer cell lines. We queried our Btz-R expression profiles against the CMAP data base and developed a correlation analysis to identify potential drugs that would be predicted to show toxicity to Btz-R lines. We identified HDAC-inhibitor and topoisomerase-inhibitor sensitivity profiles that were able to predict Btz-R tumor responsiveness to these drugs in vitro. 2) We found that Btz-R was associated with loss of PC maturation markers (CD69, CD93, BLIMP, CXCR4, spliced XBP-1), and were able to re-sensitize Btz-R cells to Btz sensitivity by inducing PC maturation. The correlation of expression markers we identified stratified survival outcomes in bortezomib containing clinical trials; thus demonstrating the markers we identified in the in vitro modeling are relevant to patient outcomes. 3) Finally, we designed a cell-based high throughput drug screening approach that led to the identification of several chemical structures with selective activity against Btz-R cells. Topoisomerase-inhibitors were among the top hits, a finding that independently supported our CMAP screening results. We also identified a more novel chemical lead (Velcade Re-sensitizing Compound 2; VRC-2) that showed modest but significant selectivity for Btz-R cells as a single agent, and most notably, exhibited potent Btz re-sensitizing activity when the 2 drugs were combined. The Btz re-sensitizing activity of VRC-2 was confirmed using multiple human and mouse Btz-R cell lines. The initial successes of the in vitro approaches that will be presented demonstrate the value of profiling resistant tumors as a means to identify secondary therapies, and demonstrate there are powerful screening approaches that can be used to effectively treat or reverse drug resistance. Disclosures: Van Ness: Millenium Pharnaceutical: Honoraria, Research Funding; Onyx Pharmaceutical: Research Funding.

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Diterpenoid Hydroperoxides from the Far-Eastern Brown Alga Dictyota dichotoma

Australian Journal of Chemistry ◽

10.1071/ch08343 ◽

2009 ◽

Vol 62 (9) ◽

pp. 1185 ◽

Cited By ~ 8

Author(s):

Sophia A. Kolesnikova ◽

Ekaterina G. Lyakhova ◽

Anatoly I. Kalinovsky ◽

Pavel S. Dmitrenok ◽

Sergei A. Dyshlovoy ◽

...

Keyword(s):

Cell Lines ◽

Brown Alga ◽

Human Cancer ◽

Algal Species ◽

Human Cancer Cell ◽

Dictyota Dichotoma ◽

Human Cancer Cell Lines ◽

New Compounds ◽

Far Eastern ◽

First Time

Two new compounds, dictyohydroperoxide 1 and hydroperoxyacetoxycrenulide 2, (Scheme 1) containing hydroperoxyl groups rarely found in algal terpenoids were isolated from the Russian population of brown alga Dictyota dichotoma. The known compounds acetoxycrenulide 4 and squalene were also found in this algal species for the first time. Some of the isolated compounds showed moderate cytoxicity against human cancer cell lines.

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Triterpene Glycosides from the Far Eastern Sea Cucumber Thyonidium (=Duasmodactyla) kurilensis (Levin): The Structures, Cytotoxicities, and Biogenesis of Kurilosides A3, D1, G, H, I, I1, J, K, and K1

Marine Drugs ◽

10.3390/md19040187 ◽

2021 ◽

Vol 19 (4) ◽

pp. 187

Author(s):

Alexandra S. Silchenko ◽

Anatoly I. Kalinovsky ◽

Sergey A. Avilov ◽

Pelageya V. Andrijaschenko ◽

Roman S. Popov ◽

...

Keyword(s):

Sea Cucumber ◽

2D Nmr ◽

Structural Features ◽

Cytotoxic Activities ◽

Hydroxyl Groups ◽

2D Nmr Spectroscopy ◽

Esi Mass Spectrometry ◽

Branched Chain ◽

Far Eastern ◽

Carbohydrate Chains

Nine new mono-, di-, and trisulfated triterpene penta- and hexaosides, kurilosides A3 (1), D1 (2), G (3), H (4), I (5), I1 (6), J (7), K (8), and K1 (9) and two desulfated derivatives, DS-kuriloside L (10), having a trisaccharide branched chain, and DS-kuriloside M (11), having hexa-nor-lanostane aglycone with a 7(8)-double bond, have been isolated from the Far-Eastern deep-water sea cucumber Thyonidium (=Duasmodactyla) kurilensis (Levin) and their structures were elucidated based on 2D NMR spectroscopy and HR-ESI mass-spectrometry. Five earlier unknown carbohydrate chains and two aglycones (having a 16β,(20S)-dihydroxy-fragment and a 16β-acetoxy,(20S)-hydroxy fragment) were found in these glycosides. All the glycosides 1–9 have a sulfate group at C-6 Glc, attached to C-4 Xyl1, while the positions of the other sulfate groups vary in different groups of kurilosides. The analysis of the structural features of the aglycones and the carbohydrate chains of all the glycosides of T. kurilensis showed their biogenetic relationships. Cytotoxic activities of the compounds 1–9 against mouse neuroblastoma Neuro 2a, normal epithelial JB-6 cells, and erythrocytes were studied. The highest cytotoxicity in the series was demonstrated by trisulfated hexaoside kuriloside H (4), having acetoxy-groups at C(16) and C(20), the latter one obviously compensated the absence of a side chain, essential for the membranolytic action of the glycosides. Kuriloside I1 (6), differing from 4 in the lacking of a terminal glucose residue in the bottom semi-chain, was slightly less active. The compounds 1–3, 5, and 8 did not demonstrate cytotoxic activity due to the presence of hydroxyl groups in their aglycones.

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Design, Synthesis, and In Vitro Evaluation of Novel Indolyl DiHydropyrazole Derivatives as Potential Anticancer Agents

Molecules ◽

10.3390/molecules26175235 ◽

2021 ◽

Vol 26 (17) ◽

pp. 5235

Author(s):

Katharigatta N. Venugopala ◽

Mohammed Habeebuddin ◽

Bandar E. Aldhubiab ◽

Afzal Haq Asif

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Anticancer Agents ◽

Human Cancer ◽

Structural Features ◽

Synthetic Methods ◽

Potential Candidate ◽

Human Cancer Cell Lines ◽

Hybrid Molecules

Indoles derived from both natural sources or artificial synthetic methods have been known to interact with aryl hydrocarbon receptors (AhR), and exhibit anticancer activity. In light of these attractive properties, a series of hybrid molecules with structural features of indoles, i.e., those bearing a pyrazoline nucleus, were evaluated for their enhanced anticancer activity. The designed molecules were subjected to molecular docking in order to screen for potential AhR interacting compounds, and the identified indolyl dihydropyrazole derivatives were synthesized. The synthesized compounds were characterized, and their cytotoxicity was evaluated against four human cancer cell lines using the MTT assay. Based on the Glide g-score, H-bonding interactions and bonding energy of 20 candidate molecules were selected for further analysis from the 64 initially designed molecules. These candidate molecules have shown promising anti-proliferative activity against the cell lines tested. Among these candidate molecules, the compounds with hydroxy phenyl substitution on the pyrazoline ring have shown potent activity across all the tested cell lines. The designed scaffold was proven effective for screening potential candidate molecules with anticancer properties, and may be further optimized structurally for yielding the ideal anti-tumorigenic compound for the treatment of various cancers.

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Structure of Cucumariosides H5, H6, H7 and H8, Triterpene Glycosides from the Sea Cucumber Eupentacta fraudatrix and Unprecedented Aglycone with 16,22-Epoxy-group

Natural Product Communications ◽

10.1177/1934578x1100600806 ◽

2011 ◽

Vol 6 (8) ◽

pp. 1934578X1100600 ◽

Cited By ~ 5

Author(s):

Alexandra S. Silchenko ◽

Anatoly I. Kalinovsky ◽

Sergey A. Avilov ◽

Pelageya V. Andryjaschenko ◽

Pavel S. Dmitrenok ◽

...

Keyword(s):

Spectral Data ◽

Sea Cucumber ◽

Epoxy Group ◽

2D Nmr ◽

Triterpene Glycosides ◽

Sulfate Group ◽

Sea Cucumbers ◽

Far Eastern ◽

Mouse Lymphocytes ◽

Eupentacta Fraudatrix

Four new triterpene glycosides cucumariosides H5 (1), H6 (2), H7 (3) and H8 (4) along with the known cucumarioside H (5) have been isolated from the Far Eastern sea cucumber Eupentacta fraudatrix. The structures of glycosides 1–4 were elucidated on the basis of spectral data (2D NMR and MS). Glycosides 1–4 belong to the group of cucumariosides H, having branched rare pentasaccharide carbohydrate moieties with one sulfate group and 3- O-methyl-D-xylose as a terminal monosaccharide unit. Glycosides 1–3 and 5 differ from each other in structures of side chains of the aglycones, while cucumarioside H8 (4) has a novel aglycone with unprecedented 16(22)-epoxy-group, never found in the sea cucumbers glycosides. Glycosides 1–3, and 5 were cytotoxic against mouse lymphocytes and hemolytic against mouse erythrocytes. Glycoside 2 was less active in comparison with others.

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