New Pyran‐2‐ones from Alkalophilic Actinomycete,Nocardiopsis alkaliphila sp. Nov. YIM‐80379

Two new pyran‐2‐ones, nocardiopyrones A and B ( 1 and 2 , resp.), along with four known compounds, pyridinols 3 – 5 , and 1‐acetyl‐β‐carboline ( 6 ) were isolated from the alkalophilic actinomycete Nocardiopsis alkaliphila sp. nov. YIM‐80379. Their structures were established on the basis of spectroscopic analysis, CD spectra, and the quantum‐chemical ECD calculation. Pyridinols 3 – 5 were isolated from a natural source for the first time. Compounds 1 and 2 showed weak antibacterial activities against Pseudomonas aeruginosa, Enterobacter aerogenes, and Escherichia coli with MIC values of 20–48 μM . Compound 2 showed weak antimicrobial activities against Candida albicans and Staphylococcus aureus with MIC values of 24 and 48 μM , respectively.     

Three New Phenylpropanoids from the Roots of Piper taiwanense and Their Inhibitory Activities on Platelet Aggregation and Mycobacterium tuberculosis

Bioassay‐guided fractionation of the active AcOEt‐soluble fraction from the roots of Piper taiwanense has led to the isolation of two new phenylpropanoids, taiwanensols A and B ( 1 and 2 , resp.), a new natural product, taiwanensol C ( 3 ), and 3‐acetoxy‐4‐hydroxy‐1‐allylbenzene ( 4 ). The compounds were obtained as two isomer mixtures ( 1 / 2 and 3 / 4 , resp.). Their structures were elucidated by spectroscopic analyses, including 1D‐ and 2D‐NMR spectroscopy and mass spectrometry, and by the comparison of their NMR data with those of related compounds. Compounds 1 – 4 were evaluated for their antiplatelet and antitubercular activities. The mixtures 1 / 2 and 3 / 4 showed potent inhibitory activities against platelet aggregation induced by collagen, with IC₅₀ values of 35.2 and 8.8 μM , respectively. In addition, 1 / 2 and 3 / 4 showed antitubercular activities against Mycobacterium tuberculosis H37Rv, with MIC values of 30.0 and 48.0 μg/ml, respectively.     

Antibacterial Δ1‐3‐Ketosteroids from the South China Sea Gorgonian Coral Subergorgia rubra

Three new Δ¹‐3‐ketosteroids characterized with a 9‐OH, subergosterones A–C ( 1 – 3 ), together with five known analogs 4 – 8 , were obtained from the gorgonian coral Subergorgia rubra collected from the South China Sea. The structures of 1 – 3 , including their absolute configurations, were determined by comprehensive spectroscopic methods and electronic circular dichroism (ECD) experiments. Compounds 2 and 3 exhibited inhibitory antibacterial activities against Bacillus cereus with MIC values of 1.56 μM .     

Bioactive Steroid Derivatives and Butyrolactone Derivatives from a Gorgonian‐Derived Aspergillus sp. Fungus

Six steroid derivatives, 1 – 6 , and five butyrolactone derivatives, 7 – 11 , were isolated from the fermentation broth of a gorgonian‐derived Aspergillus sp. fungus. Their structures were elucidated on the basis of NMR and MS spectral data. Compound 1 is a new, highly conjugated steroid. The NMR and MS data of 7 and 8 are reported for the first time, as their structures were listed in SciFinder Scholar with no associated reference. Compounds 1, 4, 5 , and 8 – 11 inhibited the larval settlement of barnacle Balanus amphitrite with EC₅₀ values ranging from 0.63 to 18.4 μg ml^?1. Butyrolactone derivatives 7 and 8 showed pronounced antibacterial activities against Staphylococcus aureus with the same MIC values as the positive control ciprofloxacin (MIC 1.56 μM for all three compounds).     

Naphthalene Derivatives and Quinones from Ventilago denticulata and Their Nitric Oxide Radical Scavenging,Antioxidant, Cytotoxic,Antibacterial, and Phosphodiesterase Inhibitory Activities

New naphthalene derivatives ( 1 and 2 ) and a new isomer ( 3 ) of ventilagolin, together with known anthraquinones, chrysophanol ( 4 ), physcion or emodin 3‐methyl ether ( 5 ), and emodin ( 6 ), were isolated from vines of Ventilago denticulata. The isolated compounds exhibited cytotoxic activity with IC₅₀ values of 1.15 – 40.54 μg/ml. Compounds 1 – 3 selectively exhibited weak antibacterial activity (MIC values of 200.0 – 400.0 μg/ml), while emodin ( 6 ) displayed moderate antibacterial activity with MIC value of 25.0 μg/ml. The isolated compounds showed nitric oxide and DPPH radical scavenging activities. Compounds 1 – 3 and 6 exhibited weak xanthine oxidase inhibitory activity, while emodin ( 6 ) acted as an aromatase inhibitor with the IC₅₀ value of 10.1 μm . Compounds 1 and 2 exhibited phosphodiesterase 5 inhibitory activity with IC₅₀ values of 8.28 μm and 6.48 μm , respectively.     

Antimicrobial Compounds from Drypetes staudtii

Antimicrobial‐directed phytochemical investigation of the MeOH extract of Drypetes staudtii afforded two new compounds, 4,5‐(methylenedioxy)‐o‐coumaroylputrescine ( 1 ), 4,5‐(methylenedioxy)‐o‐coumaroyl‐4′‐N‐methylputrescine ( 2 ), along with seven known natural products 4α‐hydroxyeremophila‐1,9‐diene‐3,8‐dione ( 3 ), drypemolundein B ( 4 ), friedelan‐3β‐ol ( 5 ), erythrodiol ( 6 ), ursolic acid ( 7 ), p‐coumaric acid ( 8 ), and β‐sitosterol ( 9 ). Structures of compounds 1 – 9 were elucidated with the aid of extensive NMR and mass spectral studies. All of the isolates exhibited antibacterial activity against Gram‐positive and Gram‐negative bacteria with minimum inhibitory concentration (MIC) in the range of 8 – 128 μg/ml. Compounds 1 – 2 were also moderately active against Candida albicans with an MIC value of 32 μg/ml.     

Antimicrobial and Cytotoxic Activity of Extracts of Ferula heuffelii Griseb. ex Heuff. and Its Metabolites

The antimicrobial and cytotoxic activities of isolates (CHCl₃ and MeOH extracts and selected metabolites) obtained from the underground parts of the Balkan endemic plant Ferula heuffelii Griseb . ex Heuff . were assessed. The CHCl₃ and MeOH extracts exhibited moderate antimicrobial activity, being more pronounced against Gram‐positive than Gram‐negative bacteria, especially against Staphylococcus aureus (MIC=12.5 μg/ml for both extracts) and Micrococcus luteus (MIC=50 and 12.5 μg/ml, resp.). Among the tested metabolites, (6E)‐1‐(2,4‐dihydroxyphenyl)‐3,7,11‐trimethyl‐3‐vinyldodeca‐6,10‐dien‐1‐one ( 2 ) and (2S*,3R*)‐2‐[(3E)‐4,8‐dimethylnona‐3,7‐dien‐1‐yl]‐2,3‐dihydro‐7‐hydroxy‐2,3‐dimethylfuro[3,2‐c]coumarin ( 4 ) demonstrated the best antimicrobial activity. Compounds 2 and 4 both strongly inhibited the growth of M. luteus (MIC=11.2 and 5.2 μM , resp.) and Staphylococcus epidermidis (MIC=22.5 and 10.5 μM , resp.) and compound 2 additionally also the growth of Bacillus subtilis (MIC=11.2 μM ). The cytotoxic activity of the isolates was tested against three human cancer cell lines, viz., cervical adenocarcinoma (HeLa), chronic myelogenous leukemia (K562), and breast cancer (MCF‐7) cells. The CHCl₃ extract exhibited strong cytotoxic activity against all cell lines (IC₅₀<11.0 μg/ml). All compounds strongly inhibited the growth of the K562 and HeLa cell lines. Compound 4 exhibited also a strong activity against the MCF‐7 cell line, comparable to that of cisplatin (IC₅₀=22.32±1.32 vs. 18.67±0.75μM ).     

Bioactive Diphenyl Ether Derivatives from a Gorgonian‐Derived Fungus Talaromyces sp.

Three new diphenyl ether derivatives, talaromycins A–C ( 1 – 3 , resp.), together with six known analogs, 4 – 9 , were isolated from a gorgonian‐derived fungus, Talaromyces sp. The structures of the new compounds were determined by analysis of extensive NMR spectroscopic data. All of the isolated metabolites, 1 – 9 , were evaluated for their cytotoxic and antifouling activities. Compound 4 exhibited pronounced cytotoxicity against the tested human cell lines with the IC₅₀ values ranging from 4.3 to 9.8 μM . Compounds 3, 5, 8 , and 9 showed potent antifouling activities against the larval settlement of the barnacle Balanus amphitrite with the EC₅₀ values ranging from 2.2 to 4.8 μg/ml.     

Cyclopentenone Derivatives and Polyhydroxylated Steroids from the Soft Coral Sinularia acuta

Four new polyhydroxylated steroids, 1 – 4 , and the racemic form of cyclopentenone 9 , together with four known steroids, 5 – 8 , one known cyclopentenone derivative, 10 , and one known butenolide derivative, 11 , were isolated from the soft coral Sinularia acuta collected from Weizhou Island of Guangxi Province, P. R. China. Their structures were elucidated on the basis of spectroscopic analyses and by comparison of the corresponding data with those previously reported. The cytotoxicities of the isolates 1 – 11 in vitro against the selected tumor cell lines HL‐60, HeLa, and K562 were evaluated. Compounds 2 and 5 showed potent cytotoxicities against HL‐60 cell lines with IC₅₀ values of 7.3 and 9.9 μM , respectively. Compounds 5 and 6 showed moderate activities against K562 cell lines with IC₅₀ values of 10.9 and 11.7 μM , respectively, while compounds 1, 2 , and 6 showed weak activities against HeLa cell lines with respective IC₅₀ values of 44.8, 27.1, and 18.2 μM . This is the first report on chemical and bioactivity research of S. acuta.     

Antifungal Bromophenols from Marine Red Alga Symphyocladia latiuscula

Three new highly brominated polyphenols, 1 – 3 , together with one known bromophenol, 4 , were isolated from the EtOH extract of a marine red alga Symphyocladia latiuscula collected from the coast of Qingdao, P. R. China. Their structures were identified by extensive spectroscopic experiments (NMR and MS) and comparison with literature data. Compounds 3 and 4 showed activities against the Candida albicans with the MIC values of 25 and 12.5 μg/ml, respectively.     

Cytotoxic Tetraprenylated Alkaloids from the South China Sea Gorgonian Euplexaura robusta

Nine achiral tetraprenylated alkaloids, including three new compounds, named malonganenones I–K ( 1 – 3 , resp.), together with six known analogs, 4 – 9 , were isolated from the gorgonian Euplexaura robusta collected from Weizhou Island of Guangxi Province, China. The structures of compounds 1 – 3 were elucidated by extensive spectral analyses, especially of their 1D‐ and 2D‐NMR data. Compounds 1, 4, 6 , and 7 showed moderate cytotoxicities against K562 and HeLa tumor cell lines with IC₅₀ values ranging from 0.35 to 10.82 μM . Compound 6 also showed moderate inhibitory activity against c‐Met kinase at a concentration of 10 μM .     

Oxygenated Cembrane Diterpenes from the South China Sea Soft Coral Sinularia tumulosa**

The chemical investigation of the rarely studied soft coral Sinularia tumulosa resulted in the discovery of five oxygenated cembrane diterpenes 1 – 5 , including two new compounds situmulins A ( 1 ) and B ( 2 ). The structures of 1 and 2 were established through the extensive analyses of 1D and 2D NMR spectral data together with the comparisons with the known compounds. Furthermore, the absolute configuration of 1 was determined by the time-dependent density functional theory (TDDFT) ECD approach, while the relative configuration of 2 was assigned via the quantum mechanical-NMR (QM-NMR) calculations. It might be worth to point out it is the first time to disclose the presence of cembrane diterpenes in the title species. In the bioassays, compound 2 not only showed strong antibacterial activities against fish pathogenic bacteria Streptococcus parauberis FP KSP28 and Phoyobacterium damselae FP2244 with both minimum inhibitory concentration for 90 % (MIC₉₀) values of 25 μM, but also demonstrated substantial inhibitory efficacy against vancomycin-resistant Enterococcus faecium bacteria G1, G4, G7, G8 and G13 from several individuals, with MIC₉₀ values of 25, 50, 100, 50 and 25 μM, respectively.     

Limonoids and Flavonoids from the Flowers of Azadirachta indica var. siamensis,and Their Melanogenesis‐Inhibitory and Cytotoxic Activities

A new limonoid, 7‐O‐acetyl‐7‐O‐debenzoyl‐22‐hydroxy‐21‐methoxylimocinin ( 2 ), and two new flavonoids, 3′‐(3‐hydroxy‐3‐methylbutyl)naringenin ( 7 ) and 4′‐O‐methyllespedezaflavanone C ( 9 ), along with nine known compounds, including two limonoids, 1 and 3 , and seven flavonoids, 4 – 6, 8 , and 10 – 12 , were isolated from a MeOH extract of the flowers of Azadirachta indica A.Juss. var. siamensis Valeton (Siamese neem tree; Meliaceae). The structures of new compounds were elucidated on the basis of extensive spectroscopic analysis and comparison with literature data. All of these compounds were evaluated for their melanogenesis‐inhibitory activities in B16 melanoma cells induced with α‐melanocyte‐stimulating hormone (α‐MSH). Compound 2 (16.9% melanin content at 30 μM ), 6‐deacetylnimbin ( 3 ; 49.6% melanin content at 100 μM ), and kaempferide ( 10 ; 41.7% melanin content at 10 μM ) exhibited inhibitory effects with no, or almost no, toxicity to the cells (81.0–111.7% cell viability). In addition, evaluation of their cytotoxic activities against HL60, A549, AZ521, and SK‐BR‐3 human cancer cell lines, isoazadironolide ( 1 ), 4′‐O‐methyl‐8‐prenylnaringenin ( 5 ), euchrestaflavanone A ( 8 ), 9 , and 3‐methoxy‐3′‐prenylnaringenin ( 12 ) revealed potent cytotoxicities against one or more cell lines with IC₅₀ values in the range of 4.5–9.9 μM .     

Four New Polyhydroxy Cyclohexanes from the Stems of Fissistigma tientangense

Four undescribed polyhydroxy cyclohexanes, fissoxhydrylenes A–D ( 1–4 ), together with two known biogenetically related polyhydroxy cyclohexanes ( 5 and 6 ) were isolated from the stems of Fissistigma tientangense Tsiang et P. T. Li. Their structures were elucidated by detailed analysis of NMR, HR-ESI-MS, IR, UV and Optical rotations data. The absolute configuration of 1 was confirmed by X-ray crystallographic. The absolute configurations of 2–4 were confirmed by chemical reaction and optical rotations. Compound 4 represent the first example of a no substituent polyhydroxy cyclohexanes from natural products. All isolated compounds were evaluated for their anti-inflammatory activities against the lipopolysaccharide-induced nitric oxide (NO) production in mouse macrophage RAW 264.7 cells in vitro. Compounds 3 and 4 showed inhibitory activities with the IC₅₀ values of 16.63±0.06 μM and 14.38±0.08 μM, respectively.     

2,5‐Diketopiperazines from the Marine‐Derived Fungus Aspergillus fumigatus YK‐7

Five new diketopiperazines, prenylcyclotryprostatin B ( 1 ), 20‐hydroxycyclotryprostatin B ( 2 ), 9‐hydroxyfumitremorgin C ( 3 ), 6‐hydroxytryprostatin B ( 4 ), and spirogliotoxin ( 5 ), were isolated from the marine‐derived fungus Aspergillus fumigatus YK‐7, along with nine known compounds, 6 – 14 . Their structures were elucidated by spectroscopic methods, and their antiproliferative effects on human leukemic monocyte lymphoma U937 and human prostate cancer PC‐3 cell lines were assessed in vitro. Compounds 10, 12 , and 13 exhibited significant cell growth‐inhibitory activities against U937 cell line, with the IC₅₀ values of 1.8, 0.2, and 0.5 μM , respectively.     

Merosesquiterpenoids and Ten‐Membered Macrolides from a Soft Coral‐Derived Lophiostoma sp. Fungus

One new merosesquiterpenoid, craterellin D ( 1 ), along with one known analog, craterellin A ( 2 ), and five known ten‐membered macrolides, 3 – 7 , were isolated from a soft coral‐derived Lophiostoma sp. fungus. The absolute configuration of 1 was established based on biogenetic consideration with the co‐isolated analog 2 , whose configuration was determined by modified Mosher's method and single‐crystal X‐ray diffraction analysis using CuK_α radiation. The absolute configuration of 3 was determined by X‐ray diffraction analysis using CuK_α radiation. Compounds 2 and 3 showed antibacterial activities against Bacillus cereus with a MIC value of 3.12 μM .     

Bioactive Pimarane Diterpenes from the Arctic Fungus Eutypella sp. D‐1

Two new pimarane diterpenes, libertellenone M ( 1 ) and libertellenone N ( 2 ), together with five known compounds were isolated from the culture extract of Eutypella sp. D‐1 derived from high‐latitude soil of the Arctic. The structures of these compounds were determined by spectroscopic data as well as experimental and calculated electronic circular dichroism (ECD) analysis. Antimicrobial and cytotoxic activities of the isolated compounds were evaluated. Compound 3 exhibited weak antibacterial activity against Escherichia coli, Bacillus subtilis, and Vibrio vulnificus, each with MIC values of 16 μg/mL. Compounds 2 and 3 showed moderate cytotoxic activity against K562 and MCF‐7 cell lines with IC₅₀ values of 7.67 and 9.57 μm , respectively.     

Two new resveratrol tetramers isolated from Cayratia japonica (Thunb.) Gagn. with strong inhibitory activity on fatty acid synthase and antioxidant activity

Two new resveratrol tetramers, cajyphenol A ( 1 ) and cajyphenol B ( 2 ), together with two known resveratrol dimers, quadrangularin A ( 3 ) and pallidol ( 4 ), and resveratrol ( 5 ) were isolated from the stems of Cayratia japonica (Thunb. ) Gagn. Their structures were established by means of NMR (¹H,¹H‐COSY, ¹H,¹³C‐HSQC, HMBC, and NOESY) and ESI‐MS analyses. Compounds 1 – 5 showed fast‐binding inhibitory activities on fatty acid synthase with the IC₅₀ values of 1.63±0.02, 1.49±0.03, 7.50±0.01, 11.1±0.01, and 10.2±0.01 μM , respectively. Compounds 1 – 5 also exhibited antioxidant activities in the ORAC assay.     

Chemical Constituents of Primulina eburnea (Gesneriaceae) and Their Cytotoxic Activities

Two new ursane-type triterpenes, eburnealactones A and B ( 1 and 2 ), one new flavonoid, eburneatin A ( 6 ), and one new phenylethanoid glycoside, chiritoside D ( 7 ), along with 9 known compounds ( 3–5 , 8–13 ) were isolated from the whole plant of Primulina eburnea. Their structures were elucidated by comprehensive spectroscopic data analysis (IR, UV, NMR, and HR-ESI-MS). All the compounds were evaluated for their cytotoxic activities. Compound 1 showed significant cytotoxic activities against MKN-45 cell lines and 5637 cell lines with the IC₅₀ values of 9.57 μM and 8.30 μM, respectively. Compound 1 exhibited moderate cytotoxic activities against A549 and PATU8988T cell lines with the IC₅₀ values of 30.70 μM and 38.22 μM, respectively. Compound 6 exhibited moderate cytotoxic activities against MKN-45, HCT116, PATU8988T, 5637 and A-673 cell lines with the IC₅₀ values of 19.69 μM, 16.44 μM, 18.07 μM, 11.51 μM and 18.15 μM, respectively. Compound 5 showed moderate cytotoxic activities against A549 cell lines with the IC₅₀ values of 24.06 μM.