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Sixteen undescribed pyrrololactam alkaloids, including five 2-bromopyrrole-ε-lactam (1a, 1b, 4a, 4b and 5), two 3-bromopyrrole-ε-lactam (9 and 10), eight pyrrole-ε-lactam (2a-3 and 6a-8), and one pyrrole-δ-lactam alkaloids (11), along with three previously reported compounds (12-14) were isolated from the marine sponge Phakellia fusca collected in the South China Sea. The planar structures were determined by NMR and MS analyses, while the absolute configurations were clearly elucidated by comparing the experimental and calculated ECD spectra. Compounds 2a, 2b, 4a-7b, 10, 12 and 13 exhibited anti-inflammatory activity in inhibiting the production of inflammatory cytokines IL-6 in LPS-induced RAW264.7 macrophages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Four new γ-lactam alkaloids, suberitolactams A-D (1-4), two new pyridine alkaloids, suberitopyridines A-B (7-8), and two known compounds (5-6) were isolated from the South China Sea sponge Pseudospongosorites suberitoides. The structures were elucidated by detailed 1D and 2D NMR experiments along with HRESIMS analysis and single crystal X-ray diffraction. Compounds 1 and 8 showed moderate to weak antiviral activity against H1 N1 virus with IC 50 values of 27.6 and 13.3 μM, respectively., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Psammocindoles A-C ( 1 - 3 ), a new class of indole alkaloids, were isolated from a Psammocinia vermis sponge. By combined spectroscopic analyses, the structures of these compounds were determined to be the indole-γ-lactams derived from three amino acid residues. In addition, an enantiomer psammocindole D ( 4 ), and the N -lactam isomers isopsammocindoles A-D ( 5 - 8 ) were also synthesized. These natural products and synthetic analogues were found to significantly stimulate adiponectin secretion in human bone marrow mesenchymal stem cells.

Six new fusarin derivatives, fusarins G-L ( 1 - 6 ), together with five known compounds ( 5 - 11 ) were isolated from the marine-derived fungus Fusarium solani 7227. The structures of the new compounds were elucidated by means of comprehensive spectroscopic methods (1D and 2D NMR, HRESIMS, ECD, and ORC) and X-ray crystallography. Compounds 5 - 11 exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by lipopolysaccharide, with IC 50 values ranging from 3.6 to 32.2 μM. The structure-activity relationships of the fusarins are discussed herein.

Linariifolioside II (1) and (2S)-2-hydroxy-5-oxoproline methyl ester (2), two new compounds along with 13 known compounds were obtained from the aerial part of Pseudolysimachion linariifolium Holub subsp. dilatatum (Nakai & Kitag.) D.Y. Hong. Their chemical structures were revealed mainly through NMR and MS data. The absolute configuration of 2 was deduced by comparing its experimental CD with the calculated ECD spectra. At a concentration of 1 mm, total antioxidant capacities of compounds 1-15 were measured using a rapid ABTS method in vitro. Compounds 1, 3-5, and 11-14 exhibited approximately equal antioxidant capacity to that of vitamin C (Vc)., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

With a combined strategy of bioinformatics analysis, gene manipulation coupled with variation of growth conditions, the targeted activation of polycyclic tetramate macrolactams (PTMs) in the deepsea-derived Streptomyces somaliensis SCSIO ZH66 was conducted, which afforded a new (1) PTM, named somamycin A, along with three enol-type tetramic acid tautomers (2-4, somamycins B-D) of 10-epi-hydroxymaltophilin, 10-epi-maltophilin and 10-epi-HSAF, respectively. The structures of compounds 1-4 were elucidated by extensive spectroscopic analyses together with ECD calculations. Compound 1 exhibited notable growth inhibition against plant pathogenic fungi Fusariumoxysporum MHKW and Alternariabrassicae BCHB with the MIC values of 1.6 and 3.1 μg/mL, respectively, which were more potent than those of the positive control nystatin; and compounds 3 and 4 displayed moderate antifungal activities. Moreover, compounds 1-4 exhibited moderate cytotoxicity against the human cancer cell lines of HCT116 and K562., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Four new phenylspirodrimane-type dimers, namely chartarlactams Q-T, along with stachyin B were isolated from the fermentation broth of a sponge-derived fungus Stachybotrys chartarum WGC-25 C-6. Chartarlactams Q-T were structurally featured by the dimerization of two units of phenylspirodrimane linked by a C-N bond. Their structures were determined on the basis of extensive spectroscopic analysis, while quantum ECD calculation and modified Mosher's method were used for the assignment of absolute configurations. Chartarlactams Q-S and stachyin B showed moderate inhibition against bacterial pathogen Staphylococcus aureus with MIC values ranging from 4 μg/mL to 16 μg/mL, and chartarlactam T exhibited significant inhibition toward ZIKV virus., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Chemical investigation of the mangrove endophytic fungus Cladosporium sp. SCNU-F0001 resulted in the isolation and identification of a new macrolide compound named thiocladospolide E (1) and a novel macrolide lactam named cladospamide A (2), along with the known cladospolide B (3). The structures were elucidated based on spectroscopic methods, and the absolute configurations were determined by X-ray diffraction and HPLC analysis after chemical derivatization. All compounds were tested for their antibacterial and cytotoxic activity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Three new 12- or 13-membered-ring macrocyclic alkaloids, named ascomylactams A-C ( 1 - 3 ), along with the analogues phomapyrrolidone C ( 4 ) and phomapyrrolidone A ( 5 ) were isolated from the mangrove endophytic fungus Didymella sp. CYSK-4. Their structures were elucidated by analysis of extensive spectroscopic data and mass spectrometric data. The structures and absolute configurations of 1 and 2 were determined by single-crystal X-ray diffraction experiments, which represents the first crystal structures described for a (6/5/6/5) tetracyclic skeleton fused with a 12- or 13-membered-ring macrocyclic moiety. The configurations of phomapyrrolidone C ( 4 ) and phomapyrrolidone A ( 5 ) were revised by detailed analysis of the NMR data. In a cytotoxic assay, compounds 1 and 3 showed moderate cytotoxicity against MDA-MB-435, MDA-MB-231, SNB19, HCT116, NCI-H460, and PC-3 human cancer cell lines, with IC 50 values in the range of 4.2-7.8 μM.

A new lactam, oligoamide ( 1 ), along with three known compounds ( 2 - 4 ), stigmasterol-3-O-β-D-glucopyranoside ( 2 ), formononetin ( 3 ) and (-)-pinitol ( 4 ) were isolated from the CH 2 Cl 2 /CH 3 OH (1:1) extract of the leaves of Angylocalyx oligophyllus by chromatographic separation. Their structures were elucidated on the basis of spectroscopic analysis (UV, IR, MS, 1D, and 2D NMR). Compound 1 was found to have weak antioxidant and urease inhibitory potential.

From an EtOAc-soluble fraction of the leaves of Azadirachta indica , one new lactam 28-norlimonoid named nimbandiolactam-21 ( 1 ), together with 2 known limonoids ( 2 and 3 ) were isolated. Their relative structures were elucidated based on NMR spectroscopic analysis. Nimbandiolactone-23 ( 2 ) showed the most potent α -glucosidase inhibitory activity, with an IC 50 value of 38.7 μM. Compound 1 represents the first naturally occurring example of a 28-norlimonoid having the lactam moiety. The plausible biosynthetic pathway for the formation of lactam moiety in 1 was proposed.

Three new polycyclic macrolactams, cyclamenols B-D (1-3), together with a known macrolactam, cyclamenol A (4), were isolated from the Streptomyces sp. OUCMDZ-4348. Their structures including absolute configurations were determined on the basis of spectroscopic analysis, chemical methods, and ECD calculations. The biosynthetic pathways involving intramolecular Diels-Alder reactions were proposed. Compound 1 exhibited selective inhibition against the gastric carcinoma cell line N87 with an IC 50 value of 10.8 μM.

In our screening program for new biologically active secondary metabolites, a new strain, Nocardiopsis CG3 (DSM 106572), isolated from the saltpan of Kenadsa, was found to produce five new polyene macrolactams, the kenalactams A-E (1-5). Their structures were elucidated by spectral methods (NMR and HRESIMS), and the absolute configuration was derived by chemical derivatization (Mosher's method). Through a feeding experiment, alanine was proven to be the nitrogen-bearing starter unit involved in biosynthesis of the polyketide kenalactam A (1). Kenalactam E (5) was cytotoxic against human prostate cancer PC-3 cells with an IC 50 value of 2.1 μM.

A sponge-associated actinomycete (strain MCCB267) was isolated from a marine sponge Mycale sp. collected in the Indian Ocean off the Southeast coast of India. Phylogenetic studies of this strain using 16S rRNA gene sequencing showed high sequence similarity to Streptomyces zhaozhouensis. However, strain MCCB267 showed distinct physiological and biochemical characteristic features and was thus designated as S. zhaozhouensis subsp. mycale. subsp. nov. A cytotoxicity-guided fractionation of the crude ethyl acetate extract of strain MCCB267 culture medium yielded four pure compounds belonging to the polycyclic tetramate macrolactam (PTM) family of natural products: ikarugamycin (IK) (1), clifednamide A (CF) (2), 30-oxo-28-N-methylikarugamycin (OI) (3), and 28-N-methylikarugamycin (MI) (4). The four compounds exhibited promising cytotoxic activity against NCI-H460 lung carcinoma cells in vitro, by inducing cell death via apoptosis. Flow cytometric analysis revealed that 1, 3, and 4 induced cell cycle arrest during G1 phase in the NCI-H460 cell line, whereas 2 induced cell arrest in the S phase. A concentration-dependent accumulation of cells in the sub-G1 phase was also detected upon treatment of the cancer cell line with compounds 1-4. The in vitro cytotoxicity studies were supported by molecular docking and molecular dynamic simulation analyses. An in silico study revealed that the PTMs can bind to the minor groove of DNA and subsequently induce the apoptotic stimuli leading to cell death. The characterization of the isolated actinomycete, the study of the mode of action of the four PTMs, 1-4, and the molecular docking and molecular dynamic simulations analyses are herein described.

A pair of enantiomeric 4-oxabicyclic[4.3.0]lactam derivatives, (+)- and (-)-penicilactam A (1), and one new polyketide derivative penicitrinone F (2) were isolated from the marine-derived fungus Penicillium griseofulvum GT-10. Their structures and absolute configurations were elucidated through extensive spectroscopic analyses combined with the calculated ECD spectra. Penicitrinone F (2) had moderate inhibitory activity towards Bacillus subtilis with a MIC value of 6.3 μM.

In search for novel antiseizure drugs (ASDs), the European FP7-funded PharmaSea project used zebrafish embryos and larvae as a drug discovery platform to screen marine natural products to identify promising antiseizure hits in vivo for further development. Within the framework of this project, seven known heterospirocyclic γ-lactams, namely, pseurotin A, pseurotin A 2 , pseurotin F1, 11- O-methylpseurotin A, pseurotin D, azaspirofuran A, and azaspirofuran B, were isolated from the bioactive marine fungus Aspergillus fumigatus, and their antiseizure activity was evaluated in the larval zebrafish pentylenetetrazole (PTZ) seizure model. Pseurotin A 2 and azaspirofuran A were identified as antiseizure hits, while their close chemical analogues were inactive. Besides, electrophysiological analysis from the zebrafish midbrain demonstrated that pseurotin A 2 and azaspirofuran A also ameliorate PTZ-induced epileptiform discharges. Next, to determine whether these findings translate to mammalians, both compounds were analyzed in the mouse 6 Hz (44 mA) psychomotor seizure model. They lowered the seizure duration dose-dependently, thereby confirming their antiseizure properties and suggesting activity against drug-resistant seizures. Finally, in a thorough ADMET assessment, pseurotin A 2 and azaspirofuran A were found to be drug-like. Based on the prominent antiseizure activity in both species and the drug-likeness, we propose pseurotin A 2 and azaspirofuran A as lead compounds that are worth further investigation for the treatment of epileptic seizures. This study not only provides the first evidence of antiseizure activity of pseurotins and azaspirofurans, but also demonstrates the value of the zebrafish model in (marine) natural product drug discovery in general, and for ASD discovery in particular.

Chemical investigation of two Irciniidae sponges collected by hand (SCUBA) from Australian near shore waters, afforded six new examples of a rare class of sesterterpene lactam; ircinialactams B (1), G (2), H (5), and I (6), and 8-hydroxyircinialactams C (3) and G (4); together with the new biosynthetically related lactone, ircinialactone A (7). Also isolated were seven biosynthetically related known Irciniidae metabolites; ircinialactams A (8) and C (9), (7E,12E,20Z,18S)-variabilin (10), (7Z,12Z,20Z,18S)-variabilin (11), (7E,12Z,20Z,18S)-variabilin (12), (7Z,12E,20Z,18S)-variabilin (13) and irciniafuran A (14). The structure elucidation of 1-14 was achieved by detailed spectroscopic analysis, and consideration of a plausible biosynthetic relationship linking Irciniidae sesterterpene β-furans, lactams and lactones., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Two new fluvirucin aglycones, named fluvirucinins C, and C2 (1-2), have been isolated from the ethyl acetate mycelial cake extract of the fermentation broth of.a marine sponge-associated actinomycete. Fluvirucinins C, (1) and C2 (2) represent a new type of 14-membered macrolactam aglycon, structurally related with the common aglycon of the known fluvirucins. Their structures were elucidated on the basis of ID and 2D NMR analyses, as well as HRESIMS experiments. The antimicrobial and cytotoxic activities of compounds 1 and 2 have been evaluated, but no significant activities found for fluvirucinins C, and C2.

A new cytotoxic agent designated isomethoxyneihumicin (1 and 2), a mixture of lactam-lactim tautomers, was isolated along with methoxyneihumicin (3) from the culture broth of the marine Nocardiopsis alba KM6-1. The structures of 1 and 2 were elucidated in spectroscopic analyses (1D and 2D NMR data, and ROESY correlations). Isomethoxyneihumicin (15.0 μM) and 3 (15.0 μM) arrested the cell cycle of Jurkat cells at the G2/M phase (66 and 67%) in 12 h. Isomethoxyneihumicin and 3 exhibited cytotoxicity against Jurkat cells with IC 50 values of 6.98 and 30.5 μM in 20 h, respectively. These results strongly suggest that isomethoxyneihumicin and 3 exhibit cytotoxicity against Jurkat cells by inhibiting the cell cycle at the G2/M phase.

Eight new γ-lactam alkaloids, hemerominors A-H (1-8), including two pair of epimers (1-4), together with six known compounds (9-14) were isolated from the roots of Hemerocallis minor Mill. The structures of 1-8 were established on the basis of extensive NMR studies and HR-MS measurements as well as comparison with literature data. The absolute configurations of 1-8 were determined by CD spectral analysis and modified Mosher's method. All of compounds were evaluated for their inhibitory effects against LPS-induced NO production in RAW264.7 macrophages. Among them, compound 13 exhibited moderate inhibitory activity against NO production and with IC 50 value of 18.0 μM., (Copyright © 2017. Published by Elsevier B.V.)

In the search for new antiprotozoal substances, hoshinolactam, an antitrypanosomal lactam, was isolated from a marine cyanobacterium. The gross structure was elucidated by spectroscopic analyses, and the absolute configuration was determined by the first total synthesis. Hoshinolactam showed potent antitrypanosomal activity with an IC 50 value of 3.9 nM without cytotoxicity against human fetal lung fibroblast MRC-5 cells (IC 50 > 25 μM).

Monascustin (1), an unusual γ-lactam, was isolated from an ethanol extract of the Monascus purpureus fermented rice. Its structure including the absolute configuration was determined by spectroscopic data analysis and confirmed by X-ray crystallography. A plausible biosynthetic pathway is discussed on the basis of amino acid derivatization. Compound 1 showed inhibitory activity against histone deacetylase 1.

Chemical investigation of Tamarix ramosissima Ledeb, a traditional herbal medicine used for rheumatoid arthritis (RA) treatment in northwest China, led to the discovery of a new phenolic aromatic rings substituted lactam, tamaractam ( 1 ), together with the previously reported compounds cis - N -feruloyl-3- O -methyldopamine ( 2 ) and trans - N -feruloyl-3- O -methyldopamine ( 3 ). The structures of the compounds were determined by high resolution electrospray ionization mass spectroscopy (HRESIMS) and 1D and 2D-NMR experiments, as well as comparison with the literature data. The effects of the three compounds on the viability of RA fibroblast-like synoviocytes (RA-FLS) were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2- H -tetrazolium bromide (MTT) assay. Pro-apoptosis effect of compound 1 in RA-FLS was further investigated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, activated caspase-3/7 level assessment using luminescence assay, and sub-G₁ fraction measurement using flow cytometry. It was found that these three compounds displayed variable proliferation inhibitory activity in RA-FLS, and compound 1 exhibited the strongest effect. Compound 1 could remarkably induce cellular apoptosis of RA-FLS, increase activated caspase-3/7 levels, and significantly increase sub-G₁ fraction in the cell cycle. The results suggested that compound 1 may inhibit the proliferation of RA-FLS through apoptosis-inducing effect, and these compounds may contribute to the anti-RA effect of T. ramosissima .

Siderophores are produced by a number of microbes to capture iron with outstandingly high affinity, which property also generates biomedical and industrial interests. Desferrioxamine E (DFO-E) secreted by streptomycetes bacteria can be an ideal candidate for iron chelation therapy, which necessitates its cost-effective production for in vitro and animal studies. This study focused on the optimization of DFO-E production by Streptomyces parvulus CBS548.68. Different combinations of various carbon and nitrogen sources as well as the addition of 3-morpholinopropane-1-sulfonic acid (MOPS) markedly affected DFO-E yields, which were attributed, at least in part, to the higher biomass productions found in MOPS-supplemented cultures. In MOPS-supplemented glucose and sodium glutamate medium, DFO-E productions as high as 2,009 ± 90 mg/l of culture medium were reached. High-performance liquid chromatography analysis demonstrated that a simple two-step purification process yielded DFO-E preparations with purities of ∼97%. Matrix assisted laser desorption ionization-time of flight mass spectrometry analysis showed that purified DFO-E always contained traces of desferrioxamine D2.

Ikarugamycin (IKA) is a previously discovered antibiotic, which has been shown to inhibit the uptake of oxidized low-density lipoproteins in macrophages. Furthermore, several groups have previously used IKA to inhibit clathrin-mediated endocytosis (CME) in plant cell lines. However, detailed characterization of IKA has yet to be performed. Consequently, we performed biochemistry and microscopy experiments to further characterize the effects of IKA on CME. We show that IKA has an IC50 of 2.7 μm in H1299 cells and acutely inhibits CME, but not other endocytic pathways, in a panel of cell lines. Although long-term incubation with IKA has cytotoxic effects, the short-term inhibitory effects on CME are reversible. Thus, IKA can be a useful tool for probing routes of endocytic trafficking., Competing Interests: The authors declare no conflicts of interests., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Four novel lactams, colletotrilactam A-D (1-4), along with six known compounds (5-10) were isolated from the culture broth of Colletotrichum gloeosporioides GT-7, a fungal endophyte of Uncaria rhynchophylla. The structures of these compounds were elucidated by comprehensive NMR spectroscopy. Isolates were tested for monoamine oxidase (MAO) inhibitory activity and compound 9 showed potent MAO inhibitory activity with IC50 value of 8.93±0.34μg/mL, when the IC50 value of iproniazid as a standard was 1.80±0.5μg/mL., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Two new compounds, designated paraphaeosphaeride D (1) and berkleasmin F (2) together with a previously known compound, berkleasmin A (3), isolated from a culture broth of the fungus Paraphaeosphaeria sp. TR-022, proved to be new circumventors of arbekacin (ABK) resistance in methicillin-resistant Staphylococcus aureus (MRSA). The structures of 1 and 2 were elucidated by spectroscopic analyses, including various NMR experiments. All compounds showed 10-100 times ABK circumvention activities using the paper disc method and reduced the MIC values of ABK against MRSA from 16 μg ml(-1) to 4 μg ml(-1) (fourfold) using the agar dilution method. These new compounds might be promising lead compounds for developing circumventors of ABK resistance in MRSA.

Crude CH2Cl2 extract from leaves of Piper laevicarpu (Piperaceae) displayed antitrypanosomal activity against trypomastigote forms of Trypanosoma cruzi (Y strain) and antimicrobial potential against Cryptococcus gattii (strain-type WM 178). Bioactivity-guided fractionation of crude extract afforded one new natural bioactive lactam derivative, named laevicarpin. The structure of isolated compound, which displayed a very rare ring system, was elucidated based on NMR, IR and MS spectral analysis. Using MTT assay, the trypomastigotes of T. cruzi demonstrated susceptibility to laevicarpin displaying IC50 value of 14.7μg/mL (49.6μM), about 10-fold more potent than the standard drug benznidazole. The mammalian cytotoxicity of laevicarpin was verified against murine fibroblasts (NCTC cells) and demonstrated a CC50 value of 100.3μg/mL (337.7μM-SI=7). When tested against Cryptococcus gattii, laevicarpin showed an IC50 value of 2.3μg/mL (7.9μM) and a MIC value of 7.4μg/mL (25μM). Based in the obtained results, laevicarpin could be used as a scaffold for future drug design studies against the Chagas disease and anti-cryptococosis agents., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The majority of antifungal compounds reported so far target the cell wall or cell membrane of fungi, suggesting that other types of antibiotics cannot exert their activity because they cannot penetrate into the cells. Therefore, if the permeability of the cell membrane could be enhanced, many antibiotics might be found to have antifungal activity. We here used the polyene antibiotic nystatin, which binds to ergosterol and forms pores at the cell membrane, to enhance the cellular permeability. In the presence of nystatin, many culture extracts from entomopathogenic fungi displayed antifungal activity. Among all the active extracts, two active components were purified and identified as helvolic acid and terramide A. Because the minimum inhibitory concentration of either compound was reduced four-fold in the presence of nystatin, it can be concluded that this screening method is useful for detecting novel antifungal activity., (Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Streptomyces xiamenensis 318, a moderate halophile isolated from a mangrove sediment, produces the anti-fibrotic compound xiamenmycin. The whole genome sequence of strain 318 was obtained through long-read single-molecule real-time (SMRT) sequencing, high-throughput Illumina HiSeq and 454 pyrosequencing technologies. The assembled genome comprises a linear chromosome as a single contig of 5,961,401-bp, which is considerably smaller than other reported complete genomes of the genus Streptomyces. Based on the antiSMASH pipeline, a total of 21 gene clusters were predicted to be involved in secondary metabolism. The gene cluster responsible for the biosynthesis of xiamenmycin resides in a strain-specific 61,387-bp genomic island belonging to the left-arm region. A core metabolic network consisting of 104 reactions that supports xiamenmycin biosynthesis was constructed to illustrate the necessary precursors derived from the central metabolic pathway. In accordance with the finding of a putative ikarugamycin gene cluster in the genome, the targeted chemical profiling of polycyclic tetramate macrolactams (PTMs) resulted in the identification of ikarugamycin. A successful genome mining for bioactive molecules with different skeletons suggests that the naturally minimized genome of S. xiamenensis 318 could be used as a blueprint for constructing a chassis cell with versatile biosynthetic capabilities for the production of secondary metabolites.

Eight new clausenamides, including three γ-lactams (1-3), four δ-lactams (4-7), and an amide (8), and seven known lactams, including compounds 9-11, which were purified from natural sources for the first time, were characterized from the leaves of Clausena lansium. Their structures were elucidated using spectroscopic methods, and the absolute configurations were determined using electronic circular dichroism and single-crystal X-ray diffraction analyses with Cu Kα radiation. Compound 2 (50 μM) protected 22.24% of cortical neurons against Aβ25-35-induced cell death.

Two new hydroxycitric acid lactone derivatives named cinatrins D (1) and E (2), and a new γ-lactam, virgaricin B (3), along with a known similar compound, virgaricin (4), were isolated from a fermentation broth of the fungus Virgaria boninensis FKI-4958. The absolute stereo structures of the new compounds were established by a combination of spectroscopic methods and chemical modifications. All three newly discovered compounds possessed weak antibacterial activity.

Dietziamides A and B, two novel tetramic acid dimers, were isolated from the rare actinomycetes Dietzia timorensis MZ-3 in the course of our HPLC-diode array screening of our collection of terrestrial actinomycetes. The spectroscopic analysis revealed the chemical structures of the first secondary metabolites characterized in the genus Dietzia. Dietziamides A and B showed moderate DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activities., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Bioassay-guided fractionation of an antimalarial DCM/MeOH extract derived from the Australian rainforest fungus Entonaema sp. resulted in the isolation of three new isoindolinone derivatives, entonalactams A-C (1-3), along with the known natural products 3-methoxy-5-methylbenzene-1,2-diol (4), daldinal B (5), and ergosta-4,6,8(14),22-tetraen-3-one (6). The chemical structures of the new secondary metabolites were determined following extensive 1D/2D NMR and MS data analysis. A single crystal X-ray structure for entonalactam A (1) confirmed the NMR-based structure assignment. Entonalactams A-C (1-3) were all determined to be racemic based on chiro-optical data. All secondary metabolites were tested in vitro against Plasmodium falciparum malaria parasites, and ergosta-4,6,8(14),22-tetraen-3-one (6) was identified as the most active compound with 66% inhibition at 50 μM., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

An endophytic fungus Paraphaeosphaeria neglecta FT462 isolated from the Hawaiian-plant Lycopodiella cernua (L.) Pic. Serm produced one unusual compound (1, paraphaeosphaeride A) with the 4-pyranone-γ-lactam-1,4-thiazine moiety, along with two new compounds (2 and 3, paraphaeosphaerides B and C, respectively) and the known compound (4). Compounds 1-3 were characterized by NMR and MS spectroscopic analysis. The absolute configuration of the 3-position of compound 1 was determined as S by electronic circular dichroism (ECD) calculations. Compound 3 also showed STAT3 inhibition at 10 μM.

One new bicyclic lactam, cladosporilactam A (1), and six known 12-membered macrolides (2-7) were isolated from a gorgonian-derived Cladosporium sp. fungus collected from the South China Sea. Their complete structural assignments were elucidated by comprehensive spectroscopic investigation. Quantum chemistry calculations were used in support of the structural determination of 1. The absolute configuration of 1 was determined by calculation of its optical rotation. Cladosporilactam A (1) was the first example of 7-oxabicyclic[6.3.0]lactam obtained from a natural source. Compound 1 exhibited promising cytotoxic activity against cervical cancer HeLa cell line with an IC50 value of 0.76 μM.

A bioassay guided fractionation of the ethyl acetate extract from culture broths of the strain Streptomyces zhaozhouensis CA-185989 led to the isolation of three new polycyclic tetramic acid macrolactams (1-3) and four known compounds. All the new compounds were structurally related to the known Streptomyces metabolite ikarugamycin (4). Their structural elucidation was accomplished using a combination of electrospray-time of flight mass spectrometry (ESI-TOF MS) and 1D and 2D NMR analyses. Compounds 1-3 showed antifungal activity against Aspergillus fumigatus, Candida albicans and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA).

A new screw lactam and two new carbohydrate derivatives, oryzalactam (1), oryzasaccharide A (2), and oryzasaccharide B (3), have been isolated from the methanol extract of rice bran together with four other known compounds, including momilactone A (4), butyl β-d-xylopyranose (5), ethyl β-d-xylopyranose (6), and methyl β-d-xylopyranose (7). The structures of these compounds were determined using a combination of spectroscopic methods and chemical analysis. This work represents the first recorded example of the isolation of compounds 1, 2, 3, 5, 6, and 7 from rice bran. The antioxidant experiments revealed that compound 1 possessed strong ABTS(+) (ABTS = 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid)) and DPPH (DPPH = diphenyl(2,4,6-trinitrophenyl) iminoazanium) radical scavenging with IC50 values of 33.38 ± 1.58 and 40.20 ± 1.34 μM, respectively. Antimicrobial assays revealed that compound 4 showed high levels of selectivity toward Escherichia coli with a minimal inhibitory concentration value of 5 μM.

Lajollamycins (1-4), each of which bears a spiro-β-lactone-γ-lactam ring and a nitro-tetraene moiety, were obtained from a marine-derived Streptomyces strain isolated from the southern area of Jeju Island, Republic of Korea. The planar structures of the lajollamycins were elucidated on the basis of spectroscopic analyses by NMR, UV, IR, and MS. The absolute configuration of lajollamycin (1), the planar structure of which has been previously reported, was determined using J-based configuration analysis based on (1)H-(1)H and (1)H-(13)C coupling constants, as well as ROESY correlations, followed by the modified Mosher's method. The absolute configurations of lajollamycins B-D (2-4) were established by comparing their CD spectra with that of 1. The lajollamycins exhibited moderate inhibitory activity toward Candida albicans isocitrate lyase.

A rare glutamine derivative, hemerocallisamine I (1), was isolated from the methanolic extract of the flower buds of daylily, together with a new pyrrole alkaloid hemerocallisamine II (2) and a new γ-lactam derivative, hemerocallisamine III (3). The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. For hemerocallisamine I (1), the absolute configuration was determined by Mo-Kα X-ray crystallographic analysis. This is the first report of a glutamine derivative with a pyrrole ring from natural plants.

Twelve new lactam-bearing limonoids, amooramides A-L (1-12), were isolated from the twigs and leaves of Amoora tsangii, and their structures fully elucidated by spectroscopic analysis. These compounds represent the first examples of rings A,B-seco-limonoids bearing unusual lactam side chains at C-17, including a 3-substituted 1,5-dihydro-2H-pyrrol-2-one moiety in 1-7 and a 4-substituted 1,5-dihydro-2H-pyrrol-2-one unit in 8-12. Compound 9 inhibited TNFα-induced NF-κB activity by 64% at a concentration of 10 μM.

Chemical investigation of fruits of Mours alba L. lead to the isolation of fifteen compounds by various chromatographies such as silica gel, Sephadex LH-20, RP-C18 column chromatography. Their structures were determined to be: 1-[5-(2-formlfuryl) methyl] dihydrogen 2-hydroxypropane-1, 2, 3-tricarboxylate 2, 3-diethyl ester (1), 1-[2-(furan-2-yl)-2-oxoethyl] pyrrolidin-2-one (2), divaricataester A (3), methyl 1-[2-(furan-2-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carboxylate (4), 1-[2-(furan-2-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carboxylic acid (5), L-pyroglutamic acid (6), L-pyroglutamic acid ethyl ester (7), 3-O-caffeoylquinic acid methyl ester (8), 3-O-caffeoylquinic acid ethyl ester (9), 5-O-caffeoylquinic acid methyl ester (10), 5-O-caffeoylquinic acid ethyl ester (11), 4-O-caffeoylquinic acid methyl ester (12), 4-O-caffeoylquinic acid methyl ester (13), 4-O-caffeoylquinic acid (14), 3-O-caffeoylquinic acid (15), respectively, based on the spectral analysis such as NMR, MS etc. Compounds 1-14 were isolated from this genus for the first time, among which 1 was a new compound.

One new gamma-lactone derivative 5-hydroxy-3-isopropyl-4-methoxyfuranone (1) and one new lactam derivative dehydrated-marinamide (2), along with two known compounds marinamide (3) and marinamide methyl ester (4) were isolated from the fermentation broth of the marine gorgonian-associated fungus Aspergillus sp. SCSGAF0093. Their structures were elucidated on the basis of spectroscopic and spectrometric analysis. Compound 1 showed significant toxicity to brine shrimp (Artemia salina) with a median lethal concentration (LC50) of 1.25 microM, and 3 inhibited protein tyrosine phosphatase 1B (PTP1B) with a half maximal inhibitory concentration (IC50) of 23.3 microg/mL.

Bioassay guided fractionation of three southern Australian marine sponges of the genus Psammocinia, selected for their ability to modulate glycine-gated chloride channel receptors (GlyRs), yielded the rare marine sesterterpenes (-)-ircinianin (1) and (-)-ircinianin sulfate (2), along with the new biosynthetically related metabolites (-)-ircinianin lactam A (3), (-)-ircinianin lactam A sulfate (4), (-)-oxoircinianin (5), (-)-oxoircinianin lactam A (6) and (-)-ircinianin lactone A (7). Acetylation of 1 returned (-)-ircinianin acetate (8). Whole cell patch-clamp electrophysiology on 1-8 established 3 as an exceptionally potent and selective α3 GlyR potentiator, and 6 as a selective α1 GlyR potentiator. The discovery and characterization of sesterterpenes 1-8, and in particular the glycinyl-lactams 3 and 6, provide valuable new insights into GlyR pharmacology. These insights have the potential to inform and inspire the development of new molecular tools to probe GlyR distribution and function, and therapeutics to treat a wide array of GlyR mediated diseases and disorders.

This review covers the literature published in 2011 for marine natural products, with 870 citations (558 for the period January to December 2011) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1152 for 2011), together with the relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.

Two new sesquiterpenoids, namely elema-1,3,7(11),8-tetraen-8,12-lactam (1) and 7β,8α-dihydroxy-1α,4αH-guai-9,11-dien-5β,8β-endoxide (2), together with five known analogs were isolated from the EtOAc extract of the rhizomes of Curcuma wenyujin. Their structures and relative configurations were determined on the basis of spectroscopic methods including 2D-NMR techniques. All compounds were tested for the inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Compound 1 showed the significant inhibitory activity with IC50 values of 9.4 µM.

A new alkaloid, stemona-lactam S, and a known alkaloid, tuberostemospiroline, were isolated from the roots of Stemona tuberosa LOUR. (Stemonaceae). Their structures and absolute stereochemistry were established by X-ray crystallography and vibrational circular dichroism.

Armeniaspiroles, a novel class of natural products isolated from Streptomyces armeniacus, are characterized by a novel spiro[4.4]non-8-ene scaffold. Various derivatives of Armeniaspiroles could be obtained by halogenation, alkylation, addition/elimination or reductions. A total synthesis of the 5-chloro analog of Armeniaspirole A has been accomplished in a linear six-step sequence. 5-Chloro-Armeniaspirole A exhibits good activity against a range of multidrug-resistant, Gram-positive bacterial pathogens., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Two unique cis-fused streptothricins (1 and 2) were isolated from the culture broth of Streptomyces sp. I08A 1776. Their structures were determined by MS, CD, and 1D and 2D NMR spectroscopic data analysis. Compound 2 showed weak antibacterial activities against Bacillus subtilis and Enterococcus faecalis with MIC values of 32 and 64 μg ml(-1), respectively.