Ju-eun Jeon

Discorhabdins from the Korean marine sponge Sceptrella sp.

Two new pyrroloiminoquinone alkaloids of the discorhabdin class, along with 12 compounds including one previously described synthetic derivative of the same and related skeletal classes, were isolated from the sponge Sceptrella sp., collected from Gageodo, Korea. The structures of these new compounds, designated as (-)-3-dihydrodiscorhabdin D (11) and (-)-discorhabdin Z (12), were determined by combined spectroscopic analyses. Compound 12 possesses an unusual hemiaminal group among the discorhabdin alkaloids. These compounds exhibited moderate to significant cytotoxicity, antibacterial activity, and inhibitory activity against sortase A.

Haliclonin A, a New Macrocyclic Diamide from the Sponge Haliclona sp.

Haliclonin A (1), a macrocyclic diamide of a novel skeletal class, was isolated from the marine sponge Haliclona sp. collected from Korean waters. The structure of this compound was determined using a combination of spectroscopic and chemical analyses. The new compound exhibited moderate cytotoxicity and antibacterial activity against diverse microbial strains.

Beta-carboline alkaloids derived from the ascidian Synoicum sp.

Six β-carboline alkaloids (1-6) of the eudistomin Y class were isolated from the Korean ascidian Synoicum sp. These compounds were chemically converted to a known compound, eudistomin Y(1) (7) and six new derivatives, designated eudistomins Y(8)-Y(13) (8-13). Several of these natural and synthetic compounds exhibited moderate to significant antimicrobial activity, weak cytotoxic activity, and inhibitory activities toward sortase A, isocitrate lyase, and Na(+)/K(+)-ATPase. Structure-activity relationships were also deduced.

Brominated aromatic furanones and related esters from the ascidian Synoicum sp.

Nine new compounds, tris-aromatic furanones (1, 2, 3a, 3b, and 4) and related bis-aromatic diesters (5a, 5b, 6a, and 6b), are described from the ascidian Synoicum sp. collected off the coast of Chuja-do, Korea. The structures of these compounds, designated as cadiolides E and G-I (1-4) and synoilides A and B (5 and 6), were determined by extensive spectroscopic analyses. The absolute configuration at the asymmetric center of cadiolide G (2) was assigned by ECD analysis. Of these new compounds, cadiolide I and the synoilides possess unprecedented carbon skeletons. Several of these compounds exhibited significant inhibition against diverse bacterial strains as well as moderate inhibition against the enzymes sortase A, isocitrate lyase, and Na(+)/K(+)-ATPase.

Polyoxygenated diterpenes from the sponge Phorbas sp.

Ten new polyoxygenated diterpenes (7-16) along with six known gagunin compounds (1-6) were isolated from the sponge Phorbas sp. collected in the Korean Sea. On the basis of a combination of NMR and mass spectroscopic analyses, the molecular structures of these diterpenes, designated as gagunins H-Q, were determined to be penta- or hexa-oxygenated diterpenes of the 10,13-bis-epi-homoverrucosane class. A new diterpene acid (17) of a bisabolane-related skeletal class was also isolated and structurally defined by the spectroscopic analyses. These compounds exhibited moderate to significant cytotoxicity against the K-562 cell line as well as weak inhibitory activity against isocitrate lyase (ICL).

Anti-inflammatory activity of compounds isolated from Astragalus sinicus L. in cytokine-induced keratinocytes and skin.

Inflammation is a part of the complex biological responses of a tissue to injury that protect the organ by removing injurious stimuli and initiating the healing process, and is considered as a mechanism of innate immunity. To identify biologically active compounds against pathogenic inflammatory and immune responses, we fractionated water, aqueous methanol and n-hexane layers from nine kinds of leguminosae and examined anti-inflammatory activity of the fractions in human keratinocytes and mouse skin. Among the fractions, rf3 and rf4, isolated from the aqueous methanol layer of Astragalus sinicus L., exhibited the strongest reactive oxygen species (ROS)-scavenging and anti-inflammatory activities as measured by inhibition of the intracellular ROS production, nuclear factor-kappaB (NF-κB), janus kinase (JAK)/signal transducer and activator of transcription (STAT), and phosphatidylinositol 3-kinase/Akt signaling in cytokine-stimulated human keratinocytes, as well as by effects on T-cell differentiation in mouse CD4+ T cells. In addition, topical application of rf3 and rf4 suppressed the progression of psoriasis-like dermatitis and expression of pro-inflammatory mediators in interleukin (IL)-23-injected mouse ears. Our results suggest that Astragalus sinicus L. may ameliorate chronic inflammatory skin diseases due to its antioxidant and anti-inflammatory activities via regulation of the intracellular ROS production, NF-κB, JAK/STAT and PI3/Akt signaling cascades as well as immune responses, and these results are the first report that Astragalus sinicus L. exhibits pharmacological activity.

Sesterterpenes from the tropical sponge Coscinoderma sp.

Eight new sesterterpenes (2, 5, and 10-15), including structurally related pentaprenyl hydroquinones (2 and 5), and seven known ones of the same structural classes were isolated from the sponge Coscinoderma sp., collected from Chuuk Island, Micronesia. On the basis of the results of combined spectroscopic analyses, the new compounds were determined to be derivatives of the halisulfates and suvanine. These compounds exhibited moderate cytotoxicity against the K562 cell line and inhibitory activities against isocitrate lyase, sortase A, and Na+/K+-ATPase; significant structure-activity relationships were evident.

Gombamide A, a Cyclic Thiopeptide from the Sponge Clathria gombawuiensis

A new peptide, gombamide A (1), was isolated from the marine sponge Clathria gombawuiensis, collected from Korean waters. On the basis of the results of combined spectroscopic analyses, the structure of this compound was determined to be a cyclic C-terminally modified thiohexapeptide containing the unusual amino acid residues para-hydroxystyrylamide (pHSA) and pyroglutamic acid (pyroGlu). The absolute configurations of all amino acid residues were determined to be l by advanced Marfeys analysis. The new compound exhibited weak cytotoxicity against A549 and K562 cell lines as well as moderate inhibitory activity against Na(+)/K(+)-ATPase.

Antimetastatic Effect of Halichondramide, a Trisoxazole Macrolide from the Marine Sponge Chondrosia corticata, on Human Prostate Cancer Cells via Modulation of Epithelial-to-Mesenchymal Transition

Halichondramide (HCA), a trisoxazole-containing macrolide isolated from the marine sponge Chondrosia corticata has been shown to exhibit cytotoxicity and antifungal activities. In our previous study, HCA was also found to exhibit antiproliferative activity against a variety of cancer cells. However, the precise mechanism of action of HCA in the antitumor activity remains to be elucidated. In the present study, we identified the antimetastatic activity of HCA in the highly metastatic PC3 human prostate cancer cells. HCA showed potent growth inhibitory activity of the PC3 cells with an IC50 value of 0.81 µM. Further analysis revealed that HCA suppressed the expression of a potential metastatic biomarker, phosphatase of regenerating liver-3 (PRL-3), in PC3 cells. The suppression of PRL-3 by HCA sequentially down-regulates the expression of phosphoinositide 3-kinase (PI3K) subunits p85 and p110. The antimetastatic effect of HCA was also correlated with the down-regulation of matrix metalloproteases (MMPs) and the modulation of cadherin switches N-cadherin and E-cadherin. In addition, HCA also effectively suppressed the migration and invasion of PC3 cells. These findings suggest that halichondramide might serve as a potential inhibitor of tumor cell metastasis with the modulation of PRL-3.

Cyclic Bis-1,3-dialkylpyridiniums from the sponge Haliclona sp.

Eight novel cyclic bis-1,3-dialkylpyridiniums, as well as two known compounds from the cyclostellettamine class, were isolated from the sponge Haliclona sp. from Korea. Structures of these novel compounds were determined using combined NMR and FAB-MS/MS analyses. Several of these compounds exhibited moderate cytotoxic and antibacterial activities against A549 cell-line and Gram-positive strains, respectively. The structure-activity relationships of cyclostellettamines are discussed based on their bioactivities.