Jongheon Shin

Hydroxy‐α‐sanshool activates TRPV1 and TRPA1 in sensory neurons

Sanshools are major active ingredients of Zanthoxylum piperitum and are used as food additives in East Asia. Sanshools cause irritant, tingling and sometimes paresthetic sensations on the tongue. However, the molecular mechanism underlying the pungent or tingling sensation induced by sanshools is not known. Because many transient receptor potential (TRP) channels are responsible for the sensations induced by various spices and food additives, we expressed 17 TRP channels in human embryonic kidney (HEK) cells and investigated their activation by hydroxy‐α‐sanshool (HαSS) or hydroxy‐β‐sanshool (HβSS) isolated from Zanthoxylum piperitum. It was found that HαSS, but not HβSS, depolarized sensory neurons with concomitant firing of action potentials and evoked inward currents. Among 17 TRP channels expressed in HEK cells, HαSS caused Ca2+ influx in cells transfected with TRPV1 or TRPA1, and evoked robust inward currents in cells transfected with TRPV1 or TRPA1. In primary cultured sensory neurons, HαSS induced inward currents and Ca2+ influx in a capsazepine‐dependent manner. Moreover, HαSS‐induced currents and Ca2+ influx were greatly diminished in TRPV1–/– mice. HαSS evoked licking behavior when injected into a single hind paw of wild‐type mice, but this was much reduced in TRPV1‐deficient mice. These results indicate that TRPV1 and TRPA1 are molecular targets of HαSS in sensory neurons. We conclude that the activations of TRPV1 and TRPA1 by HαSS explain its unique pungent, tingling sensation.

The junceellolides, new anti-inflammatory diterpenoids of the briarane class from the chinese gorgonian junceella fragilis

Abstract Four new diterpenoids, junceellolides A-D (1-4), have been isolated from the gorgonian Junceella fragilis collected in the South China Sea. The known metabolites praelolide (5) and junceellin (6) were also isolated from the same organism. The structures of the new compounds were assigned on the basis of extensive NMR analyses and by comparison with analogous spectral data from other briarane diterpenoids.

Solandelactones A-I, lactonized cyclopropyl oxylipins isolated from the hydroid Solanderia secunda

Abstract Solandelactones A-I(1–9), cyclopropyl and lactone containing novel docosanoids have been isolated from the hydroid Solanderia secunda. The structures of these compounds have been elucidated by combined spectral and chemical studies. Configuration of the cyclopropyl ring has been assigned as the opposite of related oxylipins by NOESY experiments. Absolute stereochemistry has been determined on the basis of chemical transformations and CD measurements of synthetic derivatives. In addition, the biogenetic origin of solandelactones has been discussed. Solandelactones C, D, and G exhibited moderate inhibitory activity against Farnesyl Protein Transferase.

Psammaplin A is a natural prodrug that inhibits class I histone deacetylase

Histone deacetylase (HDAC) has been highlighted as one of key players in tumorigenesis and angiogenesis. Recently, several derivatives of psammaplin (Psams) from a marine sponge have been known to inhibit the HDAC activity, but the molecular mechanism for the inhibition has not fully understood. Here, we explored the mode of action of Psams for the inhibition of HDAC activity in the molecular and cellular level. Among the derivatives, psammaplin A (Psam A) showed the potent inhibitory activity in enzyme assay and anti-proliferation assay with IC50 value of 0.003 and 1 µM, respectively. Psam A selectively induced hyperacetylation of histones in the cells, resulting in the upregulation of gelsolin, a well-known HDAC target gene, in a transcriptional level. In addition, reduced Psam A showed a stronger inhibitory activity than that of non-reduced one. Notably, glutathione-depleted cells were not sensitive to Psam A, implying that cellular reduction of the compound is responsible for the HDAC inhibition of Psam A after uptake into the cells. Together, these data demonstrate that Psam A could exhibit its activity under the reduced condition in the cells and be a new natural prodrug targeting HDAC.

Inhibition of sortase-mediated Staphylococcus aureus adhesion to fibronectin via fibronectin-binding protein by sortase inhibitors

The sortase enzymes are a family of Gram-positive transpeptidases responsible for anchoring surface protein virulence factors to the peptidoglycan cell wall layer. In Staphylococcus aureus, deletion of the sortase isoforms results in marked reduction in virulence and infection potential, making it an important antivirulence target. Recombinant sortase A (SrtA) and sortase B (SrtB) were incubated with peptide substrate containing either the LPETG or NPQTN motifs. (Z)-3-(2,5-dimethoxyphenyl)-2-(4-methoxyphenyl) acrylonitrile, β-sitosterol-3-O-glucopyranoside, berberine chloride, and psammaplin A1 showed potent inhibitory activity against SrtA and SrtB. These compounds also exhibited potent inhibitory activity against S. aureus cell adhesion to fibronectin. The fibronectin-binding activity data highlight the potential of these compounds for the treatment of S. aureus infections via inhibition of sortase activity.

New Bromotyrosine Metabolites from the Sponge Aplysinella rhax

Abstract Four new bromotyrosine metabolites (3–6) along with the previously described compounds psammaplin A (1) and bisaprasin (2) have been isolated from the sponge Aplysinella rhax collected from Guam, Palau, and Pohnpei. Based upon the results of extensive spectroscopic analysis and chemical reaction, the structures of psammaplins A1 (3) and A2 (4) have been determined to be a N,N-dimethylguanidium salt of psammaplin A sulfate and its bis-N,N-dimethylguanidium disulfate derivative, respectively. Aplysinellin A (5) possesses an additional bromotyrosine-derived C9 unit connected directly to the carbon framework of psammaplin A by a biphenylic linkage while aplysinellin B (6) is the corresponding cyclic enol ether. These compounds exhibited moderate cytotoxicity and inhibitory activities against farnesyl protein transferase and leucine aminopeptidase.

Sungsanpin, a Lasso Peptide from a Deep-Sea Streptomycete

Sungsanpin (1), a new 15-amino-acid peptide, was discovered from a Streptomyces species isolated from deep-sea sediment collected off Jeju Island, Korea. The planar structure of 1 was determined by 1D and 2D NMR spectroscopy, mass spectrometry, and UV spectroscopy. The absolute configurations of the stereocenters in this compound were assigned by derivatizations of the hydrolysate of 1 with Marfeys reagents and 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl isothiocyanate, followed by LC-MS analysis. Careful analysis of the ROESY NMR spectrum and three-dimensional structure calculations revealed that sungsanpin possesses the features of a lasso peptide: eight amino acids (-Gly(1)-Phe-Gly-Ser-Lys-Pro-Ile-Asp(8)-) that form a cyclic peptide and seven amino acids (-Ser(9)-Phe-Gly-Leu-Ser-Trp-Leu(15)) that form a tail that loops through the ring. Sungsanpin is thus the first example of a lasso peptide isolated from a marine-derived microorganism. Sungsanpin displayed inhibitory activity in a cell invasion assay with the human lung cancer cell line A549.

Petrocortynes and petrosiacetylenes, novel polyacetylenes from a sponge of the genus Petrosia

Abstract Petrocortynes A-C ( 1–3 ) and petrosiacetylenes A-D ( 4–7 ), novel long-chain polyacetylenes and related metabolites have been isolated from a sponge of the genus Petrosia . Compounds 1 and 2 are C 46 linear tetraacetylenes structurally related to petroformynes while 3 possesses an unusual γ-pyrone ring formed by an oxidative cyclization of a diacetylenic carbinol functionality. Compounds 4–7 are highly symmetric C 30 linear polyacetylenes in that 6 and 7 were isolated as unseparable mixtures of diastereomers. The structures of these compounds have been elucidated by combined chemical and spectral methods. Absolute stereochemistry has been determined by the modified Moshers method. These compounds exhibited significant brine-shrimp lethality, RNA-cleaving activity, and/or moderate inhibitory activity against PLA 2 and Na + /K + ATPase.

5-Hydroxyindole-type alkaloids, as Candida albicans isocitrate lyase inhibitors, from the tropical sponge Hyrtios sp.

Chemical investigations of the tropical marine sponge Hyrtios sp. have resulted in the isolation of a new alkaloid, 1-carboxy-6-hydroxy-3,4-dihydro-beta-carboline (1) together with the known metabolites, 6-hydroxy-3,4-dihydro-1-oxo-beta-carboline (2), 5-hydroxy-1H-indole-3-carboxylic acid methyl ester (3), serotonin (4), hyrtiosin A (5), 5-hydroxyindole-3-carbaldehyde (6), and hyrtiosin B (7). Their structures were elucidated on the basis of mass spectrometry and detailed 2D NMR spectroscopic data. Hyrtiosin B (7) displayed a potent inhibitory activity against isocitrate lyase (ICL) of Candida albicans with an IC(50) value of 89.0 microM.

Meroditerpenoids from the Brown Alga Sargassum siliquastrum

Eleven new meroditerpenoids (7-11, 14-17, 19, 20) and nine known compounds (1-6, 12, 13, 18) were isolated from the brown alga Sargassum siliquastrum. Combined chemical and spectroscopic analyses revealed a common tetraprenyl hydroquinone structure; these compounds belonged to the nahocol, isonahocol, and sargahydroquinoic acid classes. The dihydroquinone moiety of 20 was unique and unprecedented in a brown alga. Stereochemical assignments were made for several of the known compounds based on their chemical reactivity. These compounds exhibited moderate to significant radical-scavenging activity as well as weak inhibitory activities against sortase A and isocitrate lyase.