Antitubercular Sesterterpenes from the Thai Sponge <i>Brachiaster</i> sp.

Wonganuchitmeta, Saeng-ngam; Yuenyongsawad, Supreeya; Keawpradub, Niwat; Plubrukarn, Anuchit

doi:10.1021/np0498354

Cited by 51 publications

(52 citation statements)

References 9 publications

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“…So far, heteronemin has been characterized for its potentially anti-tubercular properties [45]. To our knowledge, this is the first time that anti-inflammatory as well as pro-apoptogenic activities have been described.…”

Section: Discussionmentioning

confidence: 85%

Heteronemin, a spongean sesterterpene, inhibits TNFα-induced NF-κB activation through proteasome inhibition and induces apoptotic cell death

Schumacher

Cerella

Eifes

et al. 2010

Biochemical Pharmacology

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Heteronemin, a spongean sesterterpene, inhibits TNFα-induced NF-κB activation through proteasome inhibition and induces apoptotic cell death. Biochemical Pharmacology, Elsevier, 2009, 79 (4) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 AbstractIn this study, we investigated the biological effects of heteronemin, a marine sesterterpene isolated from the sponge Hyrtios sp. on chronic myelogenous leukemia cells. To gain further insight into the molecular mechanisms triggered by this compound, we initially performed DNA microarray profiling and determined which genes respond to heteronemin stimulation in TNF-treated cells and which genes display an interaction effect between heteronemin and TNF. Within the differentially regulated genes, we found that heteronemin was affecting cellular processes including cell cycle, apoptosis, mitogen-activated protein kinases (MAPKs) pathway and the nuclear factor B (NF-B) signaling cascade.We confirmed in silico experiments regarding NF-B inhibition by reporter gene analysis, electrophoretic mobility shift analysis and IB degradation. In order to assess the underlying molecular mechanisms, we determined that heteronemin inhibits both trypsin and chymotrypin-like proteasome activity at an IC 50 of 0.4 µM.Concomitant to the inhibition of the NF-B pathway, we also observed a reduction in cellular viability. Heteronemin induces apoptosis as shown by Annexin V/propidium iodide staining, nuclear morphology analysis, procaspase 3, -8 and -9 and poly(ADPribose) polymerase (PARP) cleavage as well as truncation of Bid. Altogether, resultsshow that this compound has potential as anti-inflammatory and anti-cancer agent.

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Section: Discussionmentioning

confidence: 85%

Heteronemin, a spongean sesterterpene, inhibits TNFα-induced NF-κB activation through proteasome inhibition and induces apoptotic cell death

Schumacher

Cerella

Eifes

et al. 2010

Biochemical Pharmacology

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“…A scalarane-type bioactive sesterterpene, 12-deacetoxyscalarin 19-acetate, which was purified from the Thai sponge Brachiaster sp. (Wonganuchitmeta et al, 2004), inhibited growth of a nonvirulent strain of M. tuberculosis by 50% at MIC = 4 μM, comparing favorablywith kanamycin sulfate (MIC = 3.5 -8.5 μM). As a result of marine natural products that inhibit the mycothiol-S-conjugate amidase, a mycobacterial detoxification enzyme, several active compounds: a mixture of 1,3 pyridinium polymers isolated from the marine sponge Amphimedon sp., IC 50 = 0.1 μM; an Oceanapiside sp.-derived bromotyrosine compound, IC 50 = 3 μM and the glycosphingolipid oceanapiside, IC 50 = 10 μM.…”

Section: Antimalarial Antiprotozoal Antituberculosis and Antiplatelmentioning

confidence: 93%

Biologically active compounds from natural and marine natural organisms with antituberculosis, antimalarial, leishmaniasis, trypanosomiasis, anthelmintic, antibacterial, antifungal, antiprotozoal, and antiviral activities

Asif¹

2016

TANG [HUMANITAS MEDICINE]

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The biologically active compounds derived from different natural organisms such as animals, plants, and microorganisms like algae, fungi, bacteria and merine organisms. These natural compounds possess diverse biological activities like anthelmintic, antibacterial, antifungal, antimalarial, antiprotozoal, antituberculosis, and antiviral activities. These biological active compounds were acted by variety of molecular targets and thus may potentially contribute to several pharmacological classes. The synthesis of natural products and their analogues provides effect of structural modifications on the parent compounds which may be useful in the discovery of potential new drug molecules with different biological activities. Natural organisms have developed complex chemical defense systems by repelling or killing predators, such as insects, microorganisms, animals etc. These defense systems have the ability to produce large numbers of diverse compounds which can be used as new drugs. Thus, research on natural products for novel therapeutic agents with broad spectrum activities and will continue to provide important new drug molecules.

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“…‡ Corresponding author: E-mail: anuchit.pl@psu.ac.th which the IC 50 s were reported to be at least 10-fold more potent than that of its antitubercular activity. For examples, in our previous report [9], 1 was found to be cytotoxic with the IC 50 s in a range of 0.2-0.5 µM against a panel of cancer cell lines HeLa,and KB). It has been suggested, however, that certain chemical derivatization and/or microorganism-assisted structural transformation may improve the antitubercular activity and lower the cytotoxicity of the compounds [8].…”

Section: Introductionmentioning

confidence: 89%

“…The isolated sesterterpenes included 1 (as a major component), heteronemin acetate (2), 12-deacetyl-12-epi-19-deoxyscalarin (3), 12-epi-19-deoxyscalarin (4), and 12-deacetoxyscalarin acetate (5) [9]. The biological activities of the isolated compounds were assessed to show the antitubercular activity with the MICs in a range of 10 0 -10 2 µM, and the cytotoxicity against various cancer cell lines in a wider range of the IC 50 from 0.2 µM to virtually inactive (IC 50 s exceeding 100 fold of highest experimental concentration).…”

Section: Introductionmentioning

confidence: 99%

Structure-activity relationships of antitubercular scalaranes: Heteronemin revisited

Jaisamut

Thengyai

Yuenyongsawad

et al. 2009

Pure and Applied Chemistry

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A series of heteronemin-related antitubercular scalaranes, both from natural products and from chemical derivatization, were subjected to structure-activity investigations. Based on the activity profile, three main regions; i.e., the substituted groups hovering over C-19/C-18 and furan moiety, the functionalities in the vicinity of C-16 and the right-hand side of ring D, and the substituted groups on C-12, were speculated as the areas influencing the antitubercular activity of the scalaranes. The results suggested the promising possibility for the further investigation toward the modes of actions and/or target sites of the compounds.

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Antitubercular Sesterterpenes from the Thai Sponge Brachiaster sp.

Cited by 51 publications

References 9 publications

Heteronemin, a spongean sesterterpene, inhibits TNFα-induced NF-κB activation through proteasome inhibition and induces apoptotic cell death

Heteronemin, a spongean sesterterpene, inhibits TNFα-induced NF-κB activation through proteasome inhibition and induces apoptotic cell death

Biologically active compounds from natural and marine natural organisms with antituberculosis, antimalarial, leishmaniasis, trypanosomiasis, anthelmintic, antibacterial, antifungal, antiprotozoal, and antiviral activities

Structure-activity relationships of antitubercular scalaranes: Heteronemin revisited

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