Mycangimycin, a Polyene Peroxide from a Mutualist <i>Streptomyces</i> sp.

A mutualist actinomycete of the southern pine beetle, <i>Dendroctonus frontalis</i>, produces a polyene peroxide with pronounced antifungal activity. Its structure, absolute configuration, and biological activity were determined by spectral analysis, chemical modification followed by the modified Mosher method, and growth inhibitory assays, respectively

Sceliphrolactam, a Polyene Macrocyclic Lactam from a Wasp-Associated <i>Streptomyces</i> sp.

A previously unreported 26-membered polyene macrocyclic lactam, sceliphrolactam, was isolated from an actinomycete, <i>Streptomyces</i> sp., associated with the mud dauber, Sceliphron caementarium. Sceliphrolactam’s structure was determined by 1D- and 2D-NMR, MS, UV, and IR spectral analysis. Sceliphrolactam displays antifungal activity against amphotericin B-resistant <i>Candida albicans</i> (MIC = 4 μg/mL, 8.3 μM)

Mitochondria and DNA Targeting of 5,10,15,20-Tetrakis(7-sulfonatobenzo[<i>b</i>]thiophene) Porphyrin-Induced Photodynamic Therapy via Intrinsic and Extrinsic Apoptotic Cell Death

Photodynamic therapy (PDT) selectively targets subcellular organelles and promises an excellent therapeutic strategy for cancer treatment. Here, we report the synthesis of a new water-soluble photosensitizer, 5,10,15,20-tetrakis (7-sulfonatobenzo­[<i>b</i>]­thiophene) porphyrin (SBTP). Rational design of the porphyrinic molecule containing benzo­[<i>b</i>]­thiophene moiety at the <i>meso</i>-position led to selective accumulation in both mitochondria and nucleus of MCF-7 cells. This multitarget ability of SBTP can cause damage to mitochondria as well as DNA simultaneously. FACS analysis showed rapid cellular uptake of SBTP. High-content cell-based assay was executed to concurrently monitor increase of cytosolic Ca²⁺ levels, mitochondrial permeability transition (MPT), and caspase-3/7/8 activation in MCF-7 cells under the pathological condition caused by PDT action of SBTP. The study of cell death dynamics showed that PDT action of SBTP caused an increase in the MPT followed by an increase in cytosolic Ca²⁺ level. The localization of SBTP in the mitochondria activated the intrinsic apoptotic pathway. Additionally, localization of SBTP in the nucleus led to DNA damage in MCF-7 cells. The DNA fragmentation that occurred by PDT action of SBTP was thought to be responsible for extrinsic apoptosis of MCF-7 cells. SBTP demonstrated effective PDT activity of 5 μM IC₅₀ value to MCF-7 cells by bitargeting mitochondria and DNA

Suncheonosides A–D, Benzothioate Glycosides from a Marine-Derived <i>Streptomyces</i> sp.

A marine-derived <i>Streptomyces</i> strain, SSC21, was isolated from the sediment of Suncheon Bay, Republic of Korea. Chemical analysis of the bacterial strain resulted in the isolation of four new metabolites, suncheonosides A–D (<b>1–4</b>, respectively), each bearing a sulfur atom. The planar structures of the suncheonosides were identified as hexasubstituted benzothioate glycosides by combined spectroscopic analyses. Analysis of the configuration of the sugar moieties based on ROESY nuclear magnetic resonance correlations, one-bond ¹H–¹³C coupling constant analysis, and chemical derivatizations indicated that the suncheonosides incorporate only l-rhamnose. Suncheonosides A, B, and D promoted adiponectin production in a concentration-dependent manner during adipogenesis in human mesenchymal stem cells, suggesting antidiabetic potential

Antiviral Indolosesquiterpenoid Xiamycins C–E from a Halophilic Actinomycete

New metabolites, xiamycins C–E (<b>1</b>–<b>3</b>), were isolated from a <i>Streptomyces</i>. sp (#HK18) culture inhabiting the topsoil in a Korean solar saltern. The planar structures of the xiamycins C–E were elucidated as carbazole-bearing indolosesquiterpenoids using a combined analysis of NMR, MS, UV, and IR spectroscopic data. The absolute configurations of these new compounds were determined by analyses of NOESY and ECD data. When the xiamycins were tested for inhibitory activity on porcine epidemic diarrhea virus (PEDV), xiamycin D (<b>2</b>) showed the strongest inhibitory effect on PEDV replication (EC₅₀ = 0.93 μM) with low cytotoxicity (CC₅₀ = 56.03 μM), thus displaying a high selective index (60.31). Quantitative real-time PCR data revealed the inhibitory effect of <b>2</b> on genes encoding essential structural proteins (GP6 nucleocapsid, GP2 spike, and GP5 membrane) for PEDV replication in a dose-dependent manner. The antiviral activity of xiamycin D (<b>2</b>) was also supported by both Western blotting of the GP2 spike and GP6 nucleocapsid protein synthesis of PEDV. Therefore, xiamycin D shows the potential of indolosesquiterpenoids as new and promising chemical skeletons against PEDV-related viruses

Polyoxygenated Steroids from the Sponge <i>Clathria gombawuiensis</i>

Six new polyoxygenated steroids (<b>1</b>–<b>6</b>) along with clathriol (<b>7</b>) were isolated from the Korean marine sponge <i>Clathria gombawuiensis</i>. Based upon the results of combined spectroscopic analyses, the structures of gombasterols A–F (<b>1</b>–<b>6</b>) were elucidated to be those of highly oxygenated steroids possessing a 3β,4α,6α,7β-tetrahydroxy or equivalent (7β-sodium <i>O</i>-sulfonato for <b>3</b>) substitution pattern and a C-15 keto group as common structural motifs. The relative and absolute configurations of these steroids, including the rare 14β configuration of <b>1</b>–<b>4</b>, were determined by a combination of NOESY, <i>J</i>-based analyses, the 2-methoxy-2-(trifluoromethyl)­phenylacetic acid (MTPA) method, and X-ray crystallographic analysis. The absolute configuration of <b>7</b> was also assigned by these methods. These compounds moderately enhanced 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)­amino]-d-glucose (2-NBDG) uptake in differentiated 3T3-L1 adipocytes and phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in differentiated mouse C2C12 skeletal myoblasts

Polyoxygenated Steroids from the Sponge <i>Clathria gombawuiensis</i>

Six new polyoxygenated steroids (<b>1</b>–<b>6</b>) along with clathriol (<b>7</b>) were isolated from the Korean marine sponge <i>Clathria gombawuiensis</i>. Based upon the results of combined spectroscopic analyses, the structures of gombasterols A–F (<b>1</b>–<b>6</b>) were elucidated to be those of highly oxygenated steroids possessing a 3β,4α,6α,7β-tetrahydroxy or equivalent (7β-sodium <i>O</i>-sulfonato for <b>3</b>) substitution pattern and a C-15 keto group as common structural motifs. The relative and absolute configurations of these steroids, including the rare 14β configuration of <b>1</b>–<b>4</b>, were determined by a combination of NOESY, <i>J</i>-based analyses, the 2-methoxy-2-(trifluoromethyl)­phenylacetic acid (MTPA) method, and X-ray crystallographic analysis. The absolute configuration of <b>7</b> was also assigned by these methods. These compounds moderately enhanced 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)­amino]-d-glucose (2-NBDG) uptake in differentiated 3T3-L1 adipocytes and phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in differentiated mouse C2C12 skeletal myoblasts

Actinomadurol, an Antibacterial Norditerpenoid from a Rare Actinomycete, <i>Actinomadura</i> sp. KC 191

A new secondary metabolite, actinomadurol (<b>1</b>), was isolated along with the known compound JBIR-65 (<b>2</b>) from a rare actinomycete, <i>Actinomadura</i> strain KC 191. The structure of <b>1</b> was established as a rare member of the bacterial C-19 norditerpenoid class by NMR data and ECD calculations. The absolute configuration of <b>2</b>, which was previously reported without stereochemical analysis, was determined by using the modified Mosher’s method and ECD calculations. Actinomadurol (<b>1</b>) exhibited potent antibacterial activity against pathogenic strains, such as <i>Staphylococcus aureus</i>, <i>Kocuria rhizophila</i>, and <i>Proteus hauseri</i> (MIC = 0.39–0.78 μg/mL), whereas JBIR-65 (<b>2</b>) showed no antibacterial activity

Mohangamides A and B, New Dilactone-Tethered Pseudo-Dimeric Peptides Inhibiting <i>Candida albicans</i> Isocitrate Lyase

Mohangamides A and B (<b>1</b>–<b>2</b>) were discovered from a marine <i>Streptomyces</i> sp. collected in an intertidal mud flat. The structures of the compounds were elucidated as novel dilactone-tethered pseudodimeric peptides bearing two unusual acyl chains and 14 amino acid residues based on comprehensive spectroscopic analysis. The absolute configurations of the mohangamides were determined by chemical derivatizations, followed by chromatographic and spectroscopic analyses. Mohangamide A displayed strong inhibitory activity against <i>Candida albicans</i> isocitrate lyase

Cytotoxic Diterpenoid Pseudodimers from the Korean Sponge <i>Phorbas gukhulensis</i>

Four new cytotoxic diterpenoid pseudodimers (<b>2</b>–<b>5</b>), along with a previously reported one, gukulenin A (<b>1</b>), were isolated from the marine sponge <i>Phorbas gukhulensis</i> collected off the coast of Gagu-do, Korea. These novel compounds, designated gukulenins C–F (<b>2</b>–<b>5</b>), were determined by extensive spectroscopic analyses to be pseudodimers of the gagunins, like gukulenin A. The termini of the tropolone-containing side chains in gukulenins C–E (<b>2</b>–<b>4</b>) were found to have diverse modifications involving acetamides or taurine, whereas gukulenin F (<b>5</b>) was formed from <b>1</b> by the ring-opening of a cyclic hemiketal. The relative and absolute configurations were assigned by Murata’s and modified Snatzke’s methods using a HETLOC experiment and a CD measurement of a dimolybdenum complex, respectively. All of these compounds exhibited significant cytotoxicity against the K562 and A549 cell lines