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A thiazole-containing cyclic depsipeptide with 11 amino acid residues, named pagoamide A (1), was isolated from laboratory cultures of a marine Chlorophyte, Derbesia sp. This green algal sample was collected from America Samoa, and pagoamide A was isolated using guidance by MS/MS-based molecular networking. Cultures were grown in a light- and temperature-controlled environment and harvested after several months of growth. The planar structure of pagoamide A (1) was characterized by detailed 1D and 2D NMR experiments along with MS and UV analysis. The absolute configurations of its amino acid residues were determined by advanced Marfey’s analysis following chemical hydrolysis and hydrazinolysis reactions. Two of the residues in pagoamide A (1), phenylalanine and serine, each occurred twice in the molecule, once in the d- and once in the l-configuration. The biosynthetic origin of pagoamide A (1) was considered in light of other natural products investigations with coenocytic green algae.

Two new 1,3-benzodioxole derivatives, leucandioxoles A and B (1–2), together with two known related compounds (3–4), have been isolated from the South China Sea sponge Leucandra sp. The structures ...

The Arctic fungus Eutypella sp. D-1, previously found to produce a variety of cytotoxic cyclopropyl-fused and cyclobutyl-fused pimarane diterpenoids when grown in the defined medium, was induced to produce unusual metabolites by growing on solid rice medium. A chemical investigation on the rice medium extract led to the isolation of four new meroterpenoids, eutypellacytosporins A-D (1-4), along with the known biogenetically related compound cytosporin D (5). The structures of the new compounds were elucidated by their detailed spectroscopic analysis and modified Mosher's method. Compounds 1-4 may be formed by the 12,32-ester linkage of two moieties, cytosporin D (5) and decipienolide A or B. All isolated compounds, except 5, showed weak cytotoxicity against DU145, SW1990, Huh7, and PANC-1 cell lines with IC50 values ranging from 4.9 to 17.1 μM.

Nine new linear lipopeptides, microcolins E-M (1-9), together with four known related compounds, microcolins A-D (10-13), were isolated from the marine cyanobacterium Moorea producens using bioassay-guided and LC-MS/MS molecular networking approaches. Catalytic hydrogenation of microcolins A-D (10-13) yielded two known compounds, 3,4-dihydromicrocolins A and B (14, 15), and two new derivatives, 3,4-dihydromicrocolins C and D (16, 17), respectively. The structures of these new compounds were determined by a combination of spectroscopic and advanced Marfey's analysis. Structurally unusual amino acid units, 4-methyl-2-(methylamino)pent-3-enoic (Mpe) acid and 2-amino-4-methylhexanoic acid (N-Me-homoisoleucine), in compounds 1-3 and 8, respectively, are rare residues in naturally occurring peptides. These metabolites showed significant cytotoxic activity against H-460 human lung cancer cells with IC50 values ranging from 6 nM to 5.0 μM. The variations in structure and attendant biological activities provided fresh insights concerning structure-activity relationships for the microcolin class of lipopeptides.

Three new sesquiterpene quinones/hydroquinones, 20-demethoxy-20-isopentylaminodactyloquinone D (1), 20-demethoxy-20-isobutylaminodactyloquinone D (2), and 19-methoxy-dictyoceratin-A (3), and five k...

Two new polyketides, palitantins B and C (1 and 2), along with one known related compound (+)-palitantin (3) were obtained from the culture of the Antarctic fungus Geomyces sp. 3-1. The structures of the new compounds were elucidated by detailed analysis of HRESIMS, NMR, CD, and ECD data. Compound 3 showed potent PTP1B inhibitory activity with an IC50 value of 7.9 ��M (ursolic acid as positive control, IC50 = 8.3 ��M).

Eleganstone A (1), a rare diterpene possessing a 5/6/4/5 fused tetracyclic ring skeleton, along with its probable biogenetic precursor (2), one new dolabellane diterpene (3), and one known dolabellane diterpene (4), have been isolated from the marine sponge Dactylospongia elegans. As a pair of Z/E isomers, 2 can convert into 4 by the light-induced isomerization. Structure elucidations of all compounds were performed by spectroscopic analysis, ECD calculations, and comparison with the literature. These compounds were tested for their antibacterial and cytotoxic activities. Compounds 1–4 exhibited weak antibacterial activity against Escherichisa coli, Bacillus subtilis, and Staphylococcus aureus with MIC values of 32–64 μg/mL.

The biotransformation of total coumarins of Radix Glehniae by Lecanicillium attenuatum W-1-9 yielded three new products, lecaniside A (1), lecaniside B (2), and lecaniside C (3). The chemical structures of these metabolites were elucidated based on extensive spectral data, including 2D NMR and HRMS. The hydrogenation, dealkylation, glycosylation, and O-methylation reactions of these metabolites were observed in the present study. In the in vitro assays, compound 1 displayed a little PTP1B inhibitory activity.

Libertellenone H (LH), a marine-derived pimarane diterpenoid isolated from arctic fungus Eutypella sp. D-1, has shown effective cytotoxicity on a range of cancer cells. The present study is to explore the anticancer effect of LH on human pancreatic cancer cells and to investigate the intracellular molecular target and underlying mechanism. As shown, LH exhibited anticancer activity in human pancreatic cancer cells by promoting cell apoptosis. Mechanistic studies suggested that LH-induced reactive oxygen species (ROS) accumulation was responsible for apoptosis as antioxidant N-acetylcysteine (NAC) and antioxidant enzyme superoxide dismutase (SOD) antagonized the inhibitory effect of LH. Zymologic testing demonstrated that LH inhibited Trx system but had little effect on the glutathione reductase and glutaredoxin. Mass spectrometry (MS) analysis revealed that the mechanism of action was based on the direct conjugation of LH to the Cys32/Cys35 residue of Trx1 and Sec498 of TrxR, leading to a decrease in the cellular level of glutathione (GSH) and activation of downstream ASK1/JNK signaling pathway. Taken together, our findings revealed LH was a marine derived inhibitor of Trx system and an anticancer candidate.

Six new bromopyrrole alkaloids, longamides D–F ( 1 – 3 ), 3-oxethyl-4-[1-(4,5-dibromopyrrole-2-yl)-formamido]-butanoic acid methyl ester ( 4 ), 2-oxethyl-3-[1-(4,5-dibromopyrrole-2-yl)-formamido]-methyl propionate ( 5 ), and 9-oxethyl-mukanadin F ( 6 ), along with two known metabolites, hanishin ( 7 ) and longamide B methyl ester ( 8 ), were isolated from the South China Sea sponge Agelas sp. The racemic mixtures 1 – 5 , 7 and 8 were resolved into seven pairs of enantiomers 1a/1b – 5a/5b , 7a/7b , and 8a/8b through HPLC using a Chiralcel OJ-RH column. The structures were elucidated on the basis of spectroscopic data. The absolute configurations of each enantiomer of (±)- 1 and (±)- 2 were established through the quantum mechanical calculations of the corresponding electronic circular dichroism (ECD) spectra and using the CD exciton chirality method, respectively, whereas the absolute configurations of 3a and 3b were confirmed by comparing the experimental CD spectra with that of (−)- S -longamide B methyl ester. Individual enantiomers (+)-(9 S , 10 R )- 1a , (−)- S - 2b , (+)- R - 3a , (+)- R - 7a , and (+)- R - 8a exhibited effective antifungal activity against Candida albicans in a Caenorhabditis elegans candidiasis model.

Four new norterpene cyclic peroxides (1-4), together with three known norterpene cyclic peroxides were isolated from the Xisha Islands Sponge Diacarnus megaspinorhabdosa. Their structures were elucidated on the basis of spectroscopic analyses and comparison with the related model compounds. The compounds (1-7) were evaluated for the inhibitory activity against the malaria parasite Plasmodium falciparum, all of them showed significant antimalarial activity with IC50 values in the range of 1.6-8.6 μM.

Seven new pimarane-type diterpene derivatives, libertellenones O–S (1–5) and eutypellenones A and B (6 and 7), together with two known compounds (8 and 9), were isolated from the culture of Eutypella sp. D-1 obtained from high-latitude soil of the Arctic. Their structures were elucidated from spectroscopic data, as well as experimental and calculated electronic circular dichroism (ECD) analysis. Structurally, compounds 1–5 possess a cyclopropyl-fused pimarane diterpene moiety, whereas compounds 6 and 7 share an unusual cyclobutyl-fused pimarane diterpene skeleton. Compounds 1–9 exhibited cytotoxicities against HeLa, MCF-7, HCT-116, PANC-1, and SW1990 cells, with IC50 values in the range of 0.3 to 29.4 μM. Compounds 6 and 7 could dose-dependently inhibit the activity of NF-κB and exhibited significantly inhibitory effects on nitric oxide production induced by lipopolysaccharide.

Two new cyclohexanone derivatives, nectriatones A–B (1–2), and one new natural product, nectriatone C (3), together with three known phenolic sesquiterpene derivatives (4–6), were isolated from the culture of Nectria sp. B-13 obtained from high-latitude soil of the Arctic. The structures of all compounds were unambiguously elucidated by extensive spectroscopic analysis, as well as by comparison with the literature. These compounds were evaluated in cytotoxic and antibacterial activities. Compounds 1–6 showed cytotoxicities against SW1990, HCT-116, MCF-7, and K562 cells, with IC50 values in the range of 0.43 to 42.64 μM. Only compound 4 exhibited antibacterial activity against Escherichisa coli, Bacillus subtilis, and Staphylococcus aureus (MIC 4.0, 2.0, and 4.0 μg/ml, respectively).

(±)-Quassidines I (1) and J (2), two pairs of new bis-β-carboline alkaloid enantiomers, were isolated from the stems of Picrasma quassioides. Their structures were determined by the analysis of spectroscopic data, including HRESIMS and 2D NMR, and confirmed by single-crystal X-ray diffraction analysis. The racemic mixtures of 1 and 2 were resolved into two pairs of enantiomers, (+)-S-1a and (-)-R-1b and (+)-S-2a and (-)-R-2b, by HPLC using a chiral Daicel IB-3 column, respectively, which represents the first successful example to resolve bis-β-carboline racemic mixtures. The absolute configurations of the two pairs of enantiomers were determined by comparison between the calculated and experimental ECD spectra. The cytotoxicity evaluation revealed that (+)-S-1a and (+)-S-2a showed more potent cytotoxicity against human cervical HeLa and gastric MKN-28 cancer cell lines with IC50 values of 4.03-6.30 μM than their enantiomers with IC50 values of 9.64-12.3 μM; however, the two (+)-S-quassidines showed similar activities to their enantiomers against the mouse melanoma B-16 cancer cell line.

An unusual meroterpenoid, dysidinoid A (1), was isolated from the South China Sea sponge Dysidea sp. Its structure was elucidated by extensive spectroscopic methods including HRESIMS and 2D NMR, and its absolute configuration was determined by single-crystal X-ray diffraction analysis. Dysidinoid A (1) is the first meroterpenoid from Nature bearing a 9,4-friedodrime skeleton and a 2,5-dionepyrrole unit. Dysidinoid A (1) showed potent antibacterial activity against two strains of pathogenic bacteria methicillin-resistant Staphylococcus aureus (MRSA) with MIC90 values of 8.0 μg/mL against both.

A new furanone derivative, butanolide A (1), and a new sesquiterpene, guignarderemophilane F (2), together with six known compounds, were isolated from the fungus Penicillium sp. S-1-18 derived from Antarctic marine. The new structures were determined by spectroscopic studies such as 1D- and 2D-NMR and MS analyses. The absolute configuration of 1 was determined by the modified Mosher’s method, while the absolute configuration of 2 was determined by calculated ECD spectroscopy. The isolated secondary metabolites were evaluated for their protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. Compound 1 showed moderate inhibitory activity against PTP1B with IC50 value of 27.4 μM.

Nine new sesquiterpene quinones/hydroquinones (1–7, 10, and 12), three solvent-generated artifacts (8, 9, and 11), and three known compounds, 5-epi-smenospongine (13), smenospongine (14), and smenospongiadine (15), were isolated from the marine sponge Spongia pertusa Esper. The planar structures of the new compounds were elucidated on the basis of spectroscopic analyses. Their absolute configurations were determined by comparison between the calculated and experimental ECD spectra. In the cytotoxicity bioassay, compounds 13–15 exhibited activities against the human cancer cell lines U937, HeLa, and HepG2, with most potent cytotoxicities to U937 cells with IC50 values of 2.8, 1.5, and 0.6 μM, respectively. In addition, compound 6 displayed CDK-2 affinity with a Kd value of 4.8 μM in a surface plasmon resonance assay.

We isolated and identified a new sesquiterpene lactone which we named eut-Guaiane sesquiterpene (1), along with four cytochalasins from the fungus Eutypella sp. derived from the soil of high latitude of Arctic. The new structure was determined by spectroscopic studies such as 1D and 2D NMR and MS analyses, while the known compounds were identified by comparison of the NMR data with those in literatures. New compound 1 exhibited strong antibacterial activity against Escherichia coli, Bacillus subtilis and Staphylococcus aureus. Besides, it showed a little cytotoxicity against SGC7901 cell line.

Trip-step infrared spectroscopy, Fourier transform infrared spectroscopy combined with second derivative infrared spectroscopy (SD-IR) and two-dimensional correlation infrared spectroscopy (2DCOS-IR), was employed to characterize and discriminate nine China sponges. Sponges from different classes and different orders had respective unique IR macro-fingerprints. Their IR spectra suggested that the prime ingredient of calcareous sponges was calcium carbonate in calcite and/or aragonite forms, but that of demosponges was protein. Particularly, the sponges from the same genus which could not be identified by traditional spicule identification have been definitely discriminated. For sponges having highly similar chemical profile (IR spectral profile), SD-IR and 2DCOS-IR have been applied to enhance the spectral resolution to distinguish the sponges convincingly.

Convenient and efficient one pot method for the synthesis of 2,5-disubstituted-1,3,4-oxadiazoles based on the reaction of N,N-dimethyl amides with acid hydrazides has been developed. The methodology is applied to a wide range of difference aryl hydrazide and difference N,N-dimethyl amides to 2,5-disubstituted-1,3,4-oxadiazoles yield the in good to excellent yields. It will be possible wide useful application in synthesis.

Stannous chloride dihydrate is used as an efficient catalyst in reductive cyclization of 2-nitro-5-substituted aniline Schiff base leading to stable 2,5-disubstitued benzimidazole derivatives in excellent yields with good purity. It provides a novel method of synthesis of 2,5-disubstitued benzimidazole under reductive system at room temperature.

Fifteen polyketides, including the first hydroxylated plakortone (12) and plakdiepoxide (15), the first polyketide to embed a vicinal diepoxide, have been isolated from the Chinese sponge Plakortis simplex. The structures of the new metabolites were elucidated by analysis of spectroscopic data, Mosher’s derivatization, and DFT computational calculations. The reactivity of the major endoperoxide of this sponge was investigated, suggesting that furan, furanylidene, and plakilactone derivatives, well-known classes of natural products, could actually be chemical degradation products. Plakdiepoxide is a potent and selective modulator of peroxisome proliferator-activated receptor (PPAR)-γ, while the diunsaturated C12 fatty acid monotriajaponide (13) activates both PPAR-α and PPAR-γ, a dual activity of potential great importance for the treatment of metabolic disorders.

Three new aaptamine derivatives (1–3), together with six known related compounds (4–9), have been isolated from the South China Sea sponge Aaptos aaptos. The structures of all compounds were unambiguously elucidated on the basis of spectroscopic analyses. Compounds 1, 4, 5, 7, and 9 showed cytotoxic activities against HeLa, K562, MCF-7, and U937 cell lines with IC50 values in the range of 0.90–12.32 μM.

Two novel polyketides, simplextones A (1) and B (2), were isolated from the sponge Plakortis simplex. Their structures were established by spectroscopic methods. The absolute configurations were assigned by modified Mosher's method, X-ray crystallographic analysis, and quantum mechanical calculation of the electronic circular dichroism (ECD) spectrum. Compounds 1 and 2 featured an unprecedented polyketide skeleton via the connection of a single carbon-carbon bond to form a cyclopentane. These compounds also exhibited moderate cytotoxicity.

A series of 1-acyl-3-(2'-aminophenyl) thiourea derivatives were designed and synthesized. The structures of all the newly synthesized compounds were identified by IR, elemental analysis, 1H-NMR and 13C-NMR. Their anti-intestinal nematode activities against Nippostrongylus brazilliensis were evaluated in rats by an oral route. Among these compounds, at concentrations of 10 mg/kg of rat, compound (1-(2'-furanyl)acyl-3- (2'-aminophenyl) thiourea) (5h) produced the highest activity with 89.4% deparasitization. The present work suggests that 1-acyl-3-(2'-aminophenyl) thiourea derivatives may become useful lead compounds for anti-intestinal nematode treatment.

Four new macrocyclic lactones, bryostatin 21 (1) and 9-O-methylbryostatins 4, 16, and 17 (2-4), together with three known related compounds, bryostatins 4, 16, and 17 (5-7), have been isolated from an extract of the South China Sea bryozoan Bugula neritina. The structures of all compounds were unambiguously elucidated using detailed spectroscopic analysis. Structurally, the presence of a single methyl group at C-18 in compound 1 has not been observed before for known bryostatins. The isolated macrolides exhibited inhibitory effects against a small panel of human cancer cell lines.

Convenient and efficient one pot method for the synthesis of 2,5-disubstituted-1,3,4-oxadiazoles based on the reaction of N,N-dimethyl amides with acid hydrazides has been developed. The methodology is applied to a wide range of difference aryl hydrazide and difference N,N-dimethyl amides to 2,5-disubstituted-1,3,4-oxadiazoles yield the in good to excellent yields. It will be possible wide useful application in synthesis.

Nine new aaptamine derivatives (1–9), together with three known related compounds (10–12), have been isolated from the South China Sea sponge Aaptos aaptos. The structures of all compounds were unambiguously elucidated on the basis of spectroscopic analyses. Structurally, compound 1 possesses a piperidinyl group fused to a demethyl(oxy)aaptamine moiety, whereas compounds 3–6 share an imidazole-fused 1H-benzo[de][1,6]naphthyridin-2(4H)-one skeleton. The cytotoxic activities of the compounds were evaluated against various human cancer cell lines, and compounds 2, 8, 11, and 12 showed potent cytotoxicities against HL60, K562, MCF-7, KB, HepG2, and HT-29 cells, with IC50 values in the range of 0.03 to 8.5 μM.

Dysideanones A-C (1-3), three unusual sesquiterpene quinones with unprecedented carbon skeletons, were isolated from the South China Sea sponge Dysidea avara. Their structures including absolute configurations were determined by a combination of spectroscopic analyses and calculated ECD spectra. Within the sesquiterpene quinone structures, dysideanones A (1) and B (2) share an unprecedented 6/6/6/6-fused tetracyclic carbon skeleton, while dysideanone C (3) possesses an unusual 6/6/5/6-fused tetracyclic core. Dysideanone B (2) showed cytotoxicity against two human cancer cell lines, HeLa and HepG2, with IC50 values of 7.1 and 9.4 μM, respectively.

A series of benzonaphthyridine derivatives bearing the C=N linkage moiety were designed and synthesized. The structures of all the newly synthesized compounds were identified by elemental analysis, 1 H-NMR, 13 C-NMR and MS. Their anti-intestinal nematode activities against Nippostrongylus brazilliensis were evaluated in vivo by an oral route in male rats. Among these compounds, at concentrations of 10 mg/kg of rat, the compound 7-chloro-2-methoxy-10-(4-(4'-(1H-indol-5'-yl)methylene)aminophenyl)- amino-benzo(b)(1,5) naphthyridine (4n) produced the highest activity, with 80.2% deparasitization. These compounds may find usefulness in the discovery and development of new anti-intestinal drugs.