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Misuse of antibiotics led to the world wide spread of antimicrobial resistance threatening human lives. The notable resistance of bacterial cells to antibiotics and immune system is the difficulty associated with biofilm-linked illnesses. Natural products from plant origin with antibiofilm activity could provide more therapeutic activity with fewer adverse effects. Carissa L. is a potential drug candidate that can be considered as an agro-food waste sustainable virulence inhibitor source. This mini-review sheds light on recent studies dealing with the anti-virulence potential of Carissa species and its different mechanisms of action. The traced articles revealed that Carissa species exhibited potent antibiofilm, anti-quorum sensing, hyaluronidase inhibitory and anti-adhesion potentials, in addition to violacein, and swimming motility inhibition activities. Ursolic acid, oleanolic acid, and methyl oleanate are the main phytoconstituents of Carissa with claimed virulence inhibitory potentials. Carissa species are safe, valuable, and effective anti-virulence drugs suppressing pathogenicity when compared to conventional antibiotics.

A combination of LC-MS/MS and feature-based molecular networking analyses led to the isolation of a new adenopeptin analog, higapeptin (1), and four known peptides, adenopeptin (2), adenopeptins B and C (3 and 4), and acremopeptin (5), from the rice culture of the fungus Acremonium persicinum (18F04103) isolated from a mud flat of the Ariake Sea in Kyushu, Japan. The structure of 1 was determined by NMR and MS/MS fragmentation analyses. The absolute configuration of the constituent amino acids was determined by Marfey's analysis after acid hydrolysis. The C-terminal residue was synthesized, and its absolute configuration was established by Marfey's analysis. Compounds 1 and 2 were found to inhibit mitochondrial energy metabolism, similar to efrapeptin D (6), a known mitochondrial ATPase inhibitor., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

HPLC-MS analysis revealed the presence of an unreported peptide in the extract of the marine sponge Neopetrosia sp. Its structure was determined as a tripeptide, named neopetromin ( 1 ), composed of two tyrosine and one tryptophan residues with a heteroaromatic C-N cross-link between side chains. The absolute configuration of amino acids was determined using Marfey's method after ozonolysis and hydrolysis of 1 . Compound 1 promoted vacuole fragmentation in an actin-independent manner in tobacco BY-2 cells.

Phytochemical characterisation of the polar fraction of Erigeron annuus extract led to the isolation of glycerylerigeroside ( 1 ), a unique γ-pyrone derivative. Structure of 1 was decided by intensive study of NMR and mass spectra as 3- O -[4'-((1,3-dihydroxypropan-2-yl)oxy)-β-D-glucopyranoside)]-4H-pyran-4-one, with uncommon glyceroxy side chain attached to 4' position of pyromeconic acid β -D-glucopyranoside. Antimicrobial potential of 1 was tested against Staphylococcus aureus , Salmonella enterica , and Candida albicans . Compound 1 strongly inhibited growth of Candida albicans (MIC = 17.24 µM/disc), compared to fluconazole (MIC = 16.33 µM/disc). Meanwhile, it moderately inhibited the growth of Staphylococcus aureus (MIC = 71.84 µM/disc) and Salmonella enterica (MIC = 71.84 µM/disc), as compared with thiophenicol (MIC = 14.05 µM/disc) and (MIC = 14.05 µM/disc), respectively. The binding mode of 1 with the active site of sterol 14α-demethylase (CYP51) from Candida albicans (PDB ID: 5TZ1), in combination with fluconazole, was predicted by molecular docking study and supported the antifungal activity.

Five known furofuran lignans, dia -sesamin ( 1 ), 5-methoxysesamin ( 2 ), epi -magnolin ( 3 ), kobusin ( 4 ) and yangambin ( 5 ) were isolated for the first-time from the oleo-gum resin of Commiphora wightii . This is the first report on the 13 C NMR assignments for epi -magnolin ( 3 ). Each of the isolated compounds was evaluated for its ability to inhibit MIA PaCa-2 pancreatic cancer cell line. Among them, epi -magnolin ( 3 ) displayed potential activity (IC 50 = 29 nM) compared to colchicine (IC 50 = 56 nM). 3D-flexible alignment revealed that epi -magnolin ( 3 ) has great matching with the tubulin polymerization inhibitor, colchicine. Meanwhile, docking studies exhibited that compounds 1 - 5 displayed good binding free energies against colchicine binding site (CBS) of tubulin with binding modes that were highly comparable to that of colchicine. Compounds 2 , 3 , and 5 showed superior binding free energies than colchicine (-24.37 kcal/mol). epi -Magnolin ( 3 ) showed the highest binding score against CBS. MD simulation studies confirmed the stability of epi -magnolin ( 3 ) in the active site for 200 ns. Furthermore, four online servers (Swiss ADME, pkCSM pharmacokinetics, AdmetSAR, and ProTox-II) were utilized to predict the ADMET parameters. The in-silico pharmacokinetics predictions reveled that epi -magnolin ( 3 ) has significant oral bioavailability and drug-like capabilities.Communicated by Ramaswamy H. Sarma.

Six undescribed chlorinated sesquiterpene carbamates, aaptocarbamates A-F, and a chlorinated tris-norsesquiterpene carbamate, aaptocarbamate G, were isolated from the marine sponge Aaptos sp. collected in Indonesia. Aaptocarbamates D-F and G possess tetrahydrofurans and a tetrahydrofuranone, respectively. The relative configurations of the tetrahydrofuran units were determined by the NOE correlations and DFT-based calculation of the 13 C chemical shifts. This is the first time that chlorinated terpene carbamates have been reported from natural sources. Various aaptamine derivatives have been reported from the Aaptos sponges so far, the isolation of chlorinated terpene carbamates is very rare. Aaptocarbamates A, B, and D showed 60% inhibition of the RANKL-induced formation of multinucleated osteoclasts in RAW264 macrophages at 20 μM., 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 © 2023 Elsevier Ltd. All rights reserved.)

This study evaluated the topical effect of Lepidium sativum lyophilized seed extract (LSLE) towards Sustanon-induced alopecia in male adult Wistar albino rats in vivo, compared to minoxidil topical reference standard drug (MRD). LC-MS/MS together with molecular networking was used to profile the metabolites of LSLE. LSLE treated group revealed significant changes in alopecia related biomarkers, perturbation of androgenic markers; decline in testosterone level and elevation in 5α-reductase (5-AR); decline in the cholesterol level. On the other hand, LSLE treated group showed improvement in vascular markers; CTGF, FGF and VEGF. Groups treated topically with minoxidil and LSLE showed significant improvement in hair length. LC-MS/MS profile of LSLE tentatively identified 17 constituents: mainly glucosinolates, flavonoid glycosides, alkaloids and phenolic acids. The results point to the potential role of LSLE in the treatment of alopecia through decreasing 5(alpha)-dihydrotestosterone levels. Molecular docking was attempted to evaluate the probable binding mode of identified compounds to androgen receptor (PDB code: 4K7A)., (© 2023. The Author(s).)

In spite of tremendous efforts exerted in the management of COVID-19, the absence of specific treatments and the prevalence of delayed and long-term complications termed post-COVID syndrome still urged all concerned researchers to develop a potent inhibitor of SARS-Cov-2. The hydromethanolic extracts of different parts of E. mauritanica were in vitro screened for anti-SARS-Cov-2 activity. Then, using an integrated strategy of LC/MS/MS, molecular networking and NMR, the chemical profile of the active extract was determined. To determine the optimum target for these compounds, docking experiments of the active extract's identified compounds were conducted at several viral targets. The leaves extract showed the best inhibitory effect with IC 50 8.231±0.04 μg/ml. The jatrophane diterpenes were provisionally annotated as the primary metabolites of the bioactive leaves extract based on multiplex of LC/MS/MS, molecular network, and NMR. In silico studies revealed the potentiality of the compounds in the most active extract to 3CLpro, where compound 20 showed the best binding affinity. Further attention should be paid to the isolation of various jatrophane diterpenes from Euphorbia and evaluating their effects on SARS-Cov-2 and its molecular targets., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Antiosteoclastogenic-guided screening was conducted with 120 extracts of the medicinal plants collected in Egypt that led to the selection of Artemisia judaica L. (Asteraceae). Three undescribed davanone-related terpenoids, arteperoxides A-C, were isolated from the extract with two known derivatives, hydroxydavanone and davana acid. Structural analysis revealed that arteperoxides A-C were tris-normonoterpene-sesquiterpene conjugates with peroxide bridges. Although davanone derivatives with peroxides, such as a hydroperoxyl and peroxyhemiketal groups, have been isolated from Artemisia species, arteperoxides A-C are the first variations observed to contain peroxide bridges between two terpene-derived units. The absolute configurations of arteperoxides A and B were studied based on their spectroscopic data compared with those of the semisynthetic analogs that have ether linkages. The natural and synthetic compounds were tested for the antiosteoclastogenic activity, and arteperoxide C and hydroxydavanone were more potent than other compounds at 20 μM., 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 © 2022 Elsevier Ltd. All rights reserved.)

Background and Purpose: Osteoarthritis is a degenerative joint disease without definite treatment. It is characterized by intra-articular inflammation, cartilage degeneration, subchondral bone remodeling, and joint pain. The objective of the current study was to assess the anti-osteoarthritic effect and the possible underlying mechanism of action of Crataegus sinaica extract (CSE)., Experimental Approach: Intra-articular injection of monosodium iodoacetate in the right knee joint of all rats was done except for the sham group. One week later, the anti-inflammatory efficacy of CSE (100, 200, 300 mg/kg, daily p.o) for 4 successive weeks versus ibuprofen (40 mg/kg, p.o) was assessed. Serum inflammatory cytokines; as well as weekly assessment of knee joint swelling, joint mobility, and motor coordination were done. At the end of the experiment, a histopathological investigation of the affected knee joints and an x-ray investigation were also executed., Findings / Results: CSE significantly decreased joint swelling, pain behaviors, and serum levels of TNF-α, IL6, hyaluronic acid, and CTX-II. The radiographic findings revealed almost normal joint space with normal radiodensity and diameter in CSE-treated rats. As well, the histopathological and immunohistochemical investigations of the knee joints in CSE-treated groups retained the cartilage structure of knee joints. A significant reduction in the percentage of caspase-3-stained chondrocytes and a decrease in TGF-β1 immuno-positive areas in the synovial lining and sub lining were recorded in CSE-treated rats, compared to the osteoarthritis control group., Conclusion and Implications: This study approved the chondroprotective effects of CSE, and its ability to inhibit the pain associated with osteoarthritis., Competing Interests: All authors declared no conflict of interest in this study., (Copyright: © 2022 Research in Pharmaceutical Sciences.)

Triple-negative breast cancer is one of the most aggressive breast cancer. The first therapeutic option is chemotherapy, often based on anthracycline as doxorubicin. However, chemotherapy efficacy is limited in by the presence of P-glycoprotein (Pgp), a membrane transporter protein that effluxes doxorubicin, reducing its cellular accumulation and toxicity. Inhibiting Pgp activity with effective and non-toxic products is still an open challenge. In this work, we demonstrated that the natural product Glabratephrin (Glab), a prenylated flavonoid from Tephrosia purpurea with a unique chemical structure, increased doxorubicin accumulation and cytotoxicity in triple negative breast cancer cells with high levels of Pgp, characterized by both acquired or intrinsic resistance to doxorubicin. Glab also reduced the growth of Pgp-expressing tumors, without adding significant extra-toxicities to doxorubicin treatment. Interestingly, Glab did not change the expression of Pgp, but it reduced the affinity for Pgp and the efflux of doxorubicin, as suggested by the increased Km and the reduced Vmax. In silico molecular docking predicted that Glab binds two residues (phenylalanine 322, glutamine 721) localized in the transmembrane domains of Pgp, facing the extracellular environment. Moreover, site-directed mutagenesis identified glycine 185 as a critical residue mediating the reduced catalytic efficacy of Pgp elicited by Glab. We propose Glab as an effective and safe compound able to reverse doxorubicin resistance mediated by Pgp in triple negative breast cancers, opening the way to a new combinatorial approach that may improve chemotherapy efficacy in the most refractory and aggressive breast cancer., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Anthraquinones are a major class of compounds naturally occurring in Asphodelus microcarpus. The pharmacological actions of anthraquinones in cancer cells are known to induce apoptosis or autophagy, and revert multidrug resistance. In this study, five anthraquinone-type analogs were isolated from the methanol extract of A. microcarpus leaves and identified as, emodin, rhein, physcion, aloe-emodin, and emodic acid. Among them, aloe-emodin and emodic-acid strongly inhibited the proliferation, cells-intrinsic NF-κB activity and metastatic ability of breast cancer. Although aloe-emodin inhibited p38 and ERK phosphorylation, emodic-acid more markedly inhibited JNK, in addition to p38 and ERK phosphorylation. Both aloe-emodin and emodic-acid inhibited the secretion of the pro-tumorigenic cytokines IL-1β and IL-6, and VEGF and MMP expression, and subsequently inhibited the invasive and migratory potential of 4T1 cells. Thus, our study demonstrated the effects of aloe-emodin and emodin-acid in controlling the migratory and invasive ability of 4T1 breast cancer cells, in addition to inhibiting NF-κB activity and the expression of its downstream target molecules., (© 2021. The Japanese Society of Pharmacognosy.)

Two new homodrimane sesquiterpenoids, globbatones A and B (1 and 2), and one 16-norlabdane diterpenoid, globbatone C (3), together with two new naturally occurring, (E)-labda-8(17),12-diene-15,16-olide (4) and γ-bicyclohomofarnesen-12-ol (5), and one known homodrimane sesquiterpenoid (6), nine known labdane diterpenoids (7-15), and one isospongian diterpenoid (16), were isolated from the chloroform extract of Globba sherwoodiana rhizomes. The structures of the new compounds 1-3 were elucidated based on 1D and 2D NMR and HRESIMS spectroscopic analyses. The chloroform extract of G. sherwoodiana rhizomes and 10 μM concentrations of some of its constituents 1, 3, 4, 8, 9, 12, and 14 showed the moderate anti-Vpr activities, without cytotoxic effects on the TREx-HeLa-Vpr cell line., Competing Interests: Declaration of Competing Interest The authors declare no competing final interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A new decenoic acid derivative, gelliodesinic acid, and a naturally new alkaloid, together with three known furanoterpenoids and two known indole alkaloids, were isolated from the MeOH extract of the marine sponge Gelliodes sp. collected in Vietnam. The chemical structures of the isolated compounds were determined by analyses of 1D- and 2D-NMR and MS data and by comparisons of the data with those reported in the literature. The cytotoxicity assay against HeLa, MCF-7, and A549 cancer cell lines revealed that the three known furanoterpenes exhibited cytotoxic activities with IC 50 values ranging from 23.6 to 75.5 μM against the three cell lines, and that 1H-indole-3-carboxylic acid showed cytotoxicity with an IC 50 value of 89.2 μM against A549 cancer cell lines., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Three new quassinoids, javanicinols A and B (1 and 2) and 4-keto-(16S)-methoxyjavanicin B (3), together with three known quassinoids (4-6) were isolated from the chloroform-soluble fraction of the methanol extract of the Picrasma javanica wood. The structures of 1-3 were determined by spectroscopic analyses, including 1D and 2D NMR, HRESIMS, and CD. The anti-HIV-1 viral protein R (Vpr) assay revealed that 1 and 2 exhibited potent anti-Vpr activities at 1.25 μM. Furthermore, the assay also revealed the potent anti-Vpr activities of (16R)-methoxyjavanicin B (7) and (16S)-methoxyjavanicin B (8), which were previously isolated from the Picrasma javanica wood.

Four new polyacetylene amides, siphonellamides A-D (1-4), and one new fatty amide, siphonellamide E (5), together with a known indole fatty amide (6) and callyspongamide A (7), were isolated from the Red Sea marine sponge Siphonochalina siphonella. The structures of 1-5 were elucidated by extensive analyses of their 1D- and 2D-NMR spectra and MS. The isolated compounds were assessed for their cytotoxicity against HeLa, MCF-7, and A549 cancer cell lines. Compounds 1 and 2 exhibited cytotoxic activities with IC 50 values ranging from 9.4 to 34.1 μM, while 5 was only cytotoxic to HeLa cells, with an IC 50 value of 78.4 μM. Compound 7 showed moderate cytotoxicity against all tested cell lines., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Three new polyacetylenic alcohols, siphonellanols A-C (1-3), together with two known polyacetylenic alcohols (4-5), were isolated from the CHCl 3 -soluble fraction of the methanolic extract of the marine sponge Siphonochalina siphonella, collected in Egypt. The structures of 1-3 were determined by spectroscopic analyses of their 1D-, 2D-NMR, and MS spectra and by comparisons with reported data. The cytotoxicity assay revealed that 1-3 exhibited moderate cytotoxic activities against a human cervical cancer cell line (HeLa), a human breast cancer cell line (MCF-7), and a human lung cancer cell line (A549) with IC 50 values ranging from 25.9 to 69.2 μM.

A new halicyclamine derivative, tetradehydrohalicyclamine B (1), was isolated from the marine sponge Acanthostrongylophora ingens, along with halicyclamine B (2) as proteasome inhibitors. Compound 1 is the second example found to have a pyridinium ring in the halicyclamine family. Although the relative configuration of 2 was previously determined by X-ray crystallographic analysis, here we determined the absolute configuration of 2 by ECD experiment. Compounds 1 and 2 inhibited the constitutive proteasome as well as the immunoproteasome. The inhibitory activities of 2 were 4- to 10-fold more potent than those of 1., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A new series of Schiff bases containing benzіmidazole moiety 11-17 were synthesized by the reaction of 4-(1H-benzо[d]іmіdazоl-2-yl)anіline (1) with different aromatic aldehydes (4-10) via conventional heating and microwave irradiation methods. The structures of the novel Schiff bases were characterized by using different spectral data. Also, metal complexes 18-21 of compound 13 were synthesized, and their structure was confirmed by spectral measurements (IR, NMR, UV), molar conductivity, magnetic susceptibility and thermo-gravimetric analysis. The novel synthesized ligand 13 and its complexes 18-21 were tested for their in vitro antitumor activities towards breast, liver and lung cancer cell lines. Also, the acute toxicity of the prepared compounds 13 and 18-21 was determined in vivo. The results showed that the newly synthesized compounds 13 and 18-21 exhibited a significant activity against cancer, especially for complex 21, compared to standard drug doxorubicin. The molecular docking of complexes 20 and 21 has been also studied as Aurora kinase inhibitors.

New sipholane type triterpenes, sipholenols N and O (1 and 2) and neviotine D (3), were isolated from the Red Sea marine sponge Siphonochalina siphonella along with four known triterpenes, sipholenone A (4), sipholenol A (5), siphonellinol D (6) and neviotine A (7). Structure elucidation of 1-3 was achieved by extensive 1D and 2D NMR analyses. The isolated compounds were examined for the inhibition of RANKL induced osteoclastogenesis in RAW264 macrophages. Neviotine D (3) and neviotine A (4) showed potent inhibition with IC 50 values of 12.8 and 32.8 μM, respectively., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Carissa carandas L. is known in folk medicine for its anti-inflammatory and hepatoprotective activities. Meanwhile it is an evergreen shrub that constitutes a continuous source of leaves throughout the year., Hypothesis/purpose: The leaves of Carissa carandas L. may be rich in compounds that can be used as safe anti-inflammatory and antioxidant remedies. The combined antioxidant and anti-inflammatory activities provoked the study of the hepatoprotective effects., Study Design: To isolate major constituents from the leaves of Carissa carandas L. and test their anti-inflammatory and antioxidant activities in-vivo and in-vitro., Methods: The leaves of Carissa carandas L. were extracted with 80% MeOH and then defatted with CHCl 3 to yield Carissa carandas defatted extract (CCDE). The extract was chemoprofiled using UPLC-MS/MS to stand for major constituents, then subjected to different chromatographic separation steps and naringin (NG) was isolated in a high yield. The anti-inflammatory activity of NG was investigated in-vivo by carrageenan induced hind rat paw edema model at two dose levels (50 and 25 mg/kg). The anti-inflammatory activity was also evaluated in-vitro by measuring its inhibitory effect on LPS induced release of NO from RAW 264.7 macrophages. The antioxidant activity was evaluated by superoxide and DPPH radical scavenging ability. The safety of NG was tested against primary rat hepatocytes. The hepatoprotective effect of CCDE was evaluated by detecting its effects on serum liver function markers and liver cell oxidative stress markers., Results: NG exhibited potent inhibition of inflammation as compared to indomethacin (20 mg/kg). NG inhibited LPS induced release of NO from macrophages (IC 50 , 6.4 μM). NG showed significant antioxidant activity as it scavenged the superoxide radical (EC 90 , 10.95 μM) and DPPH radical (EC 50 , 11.2 μM). CCDE inhibited the elevation of the serum liver marker enzymes and increased GSH and decreased MDA contents in the liver homogenate. Liver histopathology supported the biochemical findings., Conclusion: C. carandas has potent anti-inflammatory, antioxidant and hepatoprotective activities., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Three new spongian diterpenes, ceylonins G-I (1-3), were isolated from the marine sponge Spongia ceylonensis collected in Indonesia, together with five known spongian diterpenes (4-8). Only 4 inhibited USP7 with an IC 50 value of 8.2 μM.

Three new furanosesterterpene tetronic acids, sulawesins A-C (1-3), were isolated from a Psammocinia sp. marine sponge, along with the known compounds ircinins-1 (4) and -2 (5). Although ircinins-1 and -2 were previously isolated as (+)- or (-)-enantiomers from marine sponges, we isolated them as enantiomeric mixtures. Sulawesins A and B possess a new carbon skeleton with a 5-(furan-3-yl)-4-hydroxycyclopent-2-enone moiety and were also found to be diastereomeric mixtures of four isomers by an HPLC analysis with a chiral-phase column. Sulawesin C has a dimeric structure of ircinin-1 and is the first dimer in this family. USP7, a deubiquitinating enzyme, is an emergent target of cancer therapy, and the isolated compounds inhibited USP7 with IC 50 values in the range of 2.7-4.6 μM.

Six new spongian diterpene derivatives, ceylonins A-F (1-6), were isolated from the Indonesian marine sponge Spongia ceylonensis along with spongia-13(16),14-dien-19-oic acid (7). They contained three additional carbons in ring D to supply an ether-bridged bicyclic ring system. Their structures were elucidated by analyzing NMR spectroscopic data and calculated ECD spectra in comparison to experimental ECD spectra. The bicyclic ring system may be derived from the major metabolite 7 and a C 3 unit (an acrylic acid equivalent) through an intermolecular Diels-Alder reaction, which was experimentally supported by the formation of 1-6 from 7 and acrylic acid. The inhibitory effects of the isolated compounds on the RANKL-induced formation of multinuclear osteoclasts in RAW264 macrophages were examined.

Seven new spongian diterpenes, ceylonamides A-F (1-6) and 15α,16-dimethoxyspongi-13-en-19-oic acid (7), were isolated from the Indonesian marine sponge Spongia ceylonensis along with eight known spongian diterpenes, 8-15. Compounds 1-6 were determined to be nitrogenous spongian diterpenes. The isolated compounds were examined for the inhibition of RANKL-induced osteoclastogenesis in RAW264 macrophages. Ceylonamide A (1) exhibited the most potent inhibitory activity with an IC50 value of 13 μM, followed by ceylonamide B (2) (IC50, 18 μM). An examination of the structure-activity relationships of the isolated compounds revealed that the position of the carbonyl group of the γ-lactam ring and bulkiness of the substituent at its nitrogen atom were important for inhibitory activity.

Halenaquinone was isolated from the marine sponge Petrosia alfiani as an inhibitor of osteoclastogenic differentiation of murine RAW264 cells. It inhibited the RANKL (receptor activator of nuclear factor-κB ligand)-induced upregulation of TRAP (tartrate-resistant acid phosphatase) activity as well as the formation of multinuclear osteoclasts. In addition, halenaquinone substantially suppressed RANKL-induced IκB degradation and Akt phosphorylation. Thus, these results suggest that halenaquinone inhibits RANKL-induced osteoclastogenesis at least by suppressing the NF-κB and Akt signaling pathways., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Two new manzamine alkaloids, acantholactam (3) and pre-neo-kauluamine (4), were isolated from the marine sponge Acanthostrongylophora ingens along with manzamine A (1) and neo-kauluamine (2). Acantholactam contains a γ-lactam ring N-substituted with a (Z)-2-hexenoic acid moiety and is proposed to be biosynthetically derived from manzamine A by oxidative cleavage of the eight-membered ring. Compound 4 was converted to the dimer 2 during storage, suggesting nonenzymatic dimer formation. Among the four isolated compounds, 1, 2, and 4 showed proteasome inhibitory activity.