Novel polyhydroxysterols from the Red Sea marine sponge Lamellodysidea herbacea

Chemical investigation of the dichloromethane extract of the Red Sea marine sponge Lamellodysidea herbacea led to the isolation of four novel polyhydroxysteroids: cholesta-8-en-3beta,5alpha,6alpha,25-tetrol (1), cholesta-8(14)-en-3beta,5alpha,6alpha,25-tetrol (2), cholesta-8,24-dien-3beta,5alpha,6alpha-triol (3), and cholesta-8(14),24-dien-3beta,5alpha,6alpha-triol (4). Their structures were identified through 1D and 2D NMR studies. Relative stereochemistries were established by analysis of chemical shifts, coupling constants, and NOESY correlations. Compounds 3-4 showed antifungal activity against Candida tropicalis, with an inhibition diameter of 13 and 11 mm at 10 microg/disc, respectively.     

Bioactive metabolites from the sponge Suberea sp

Two new brominated compounds, subereaphenol K ( 2 ) and 2‐(3,5‐dibromo‐1‐ethoxy‐4‐oxocyclohexa‐2,5‐dien‐1‐yl)acetamide ( 3 ), together with subereaphenol B (methyl 2‐(2,4‐dibromo‐3,6‐dihydroxyphenyl)acetate; 1 ) with a revised structure, and five dibromotyrosine‐derived metabolites, 4 – 8 , were isolated from the sponge Suberea sp. and characterized by 1D‐ and 2D‐NMR spectroscopic and HR‐MS spectrometric data. Compounds 1, 2, 6 , and 8 exhibited various weak or moderate bioactivities, including antimicrobial and cytotoxic activities. Furthermore, compounds 1 and 2 inhibited human recombinant phosphodiesterase 4 (PDE4) with IC₅₀ values of 2 μM , whereas compounds 6 and 8 were less active.     

Terpenes from the Soft Corals Litophyton arboreum and Sarcophyton ehrenbergi

The new cembrane diterpene (3E,11E)‐cembra‐3,8(19),11,15‐tetraene‐7α‐ol ( 1 ), nephthenol ( 2 ), and all‐trans‐peridinin ( 3 ) have been isolated from the soft coral Litophyton arboreum. The tetraterpene 3 , (+)‐7,8‐epoxy‐7,8‐dihydrocembrene C ( 4 ), emblide ( 5 ), sarcophytoxide ( 6 ), sarcoglaucol‐16‐one ( 7 ), guajacophine ( 8 ), and 1,4‐peroxymuurol‐5‐ene ( 9 ) have been obtained from the soft coral Sarcophyton ehrenbergi. The compounds were characterized primarily by NMR spectroscopy. Some of the terpenes were tested for their antiproliferative activity against the cell lines HUVEC and K‐562 and for cytotoxicity against the cell line HeLa, and they showed moderate activities.     

Chemical evaluation and antibacterial activity of novel bioactive compounds from endophytic fungi in Nelumbo nucifera

The objective of this study was to characterize an endophytic fungi producing-bioactive compound from the aquatic plant, Nelumbo nucifera. All parts of such plant were cleaned with surface sterilization technique and cultured on potato dextrose agar to isolate endophytic fungi. The identification was characterized by morphological and molecular technique. Fungal isolates were screened to discover antimicrobial activities by disc diffusion method against Methicillin-resistant Staphylococcus aureus DMST20651 (MRSA). MIC and MBC for those crude fungal extracts were determined. Finally, the chemical profile of crude extract was determined by gas chromatography and mass spectrometry. Six endophytic fungi were isolated from the surface-satirized parts of N. nucifera. Based on disc diffusion assay, the highest antibacterial activity against MRSA was isolate ST9.1 identified as Aspergillus cejpii. Results demonstrated that the ethyl acetate extraction had more active fractions with MIC of 2.5 mg/ml and MBC concentration of 50.0 mg/ml. The crude extracts were developed to identify the chemical constituents by gas chromatography and mass spectrometry. The major component of crude extract of endophytic fungi was 5-(1H-Indol-3-yl)-4,5-dihydro-[1,2,4]triazin-3-ylamine (C₁₁H₁₁N₅). Thus, the plant could be used in the treatment of infectious diseases caused by bacterial pathogen.     

Fusarithioamide B,a new benzamide derivative from the endophytic fungus Fusarium chlamydosporium with potent cytotoxic and antimicrobial activities

Fusarithioamide B (6), a new aminobenzamide derivative with unprecedented carbon skeleton and five known metabolites: stigmast-4-ene-3-one (1), stigmasta-4,6,8(14),22-tetraen-3-one (2), p-hydroxyacetophenone (3), tyrosol (4), and fusarithioamide A (5) were separated from Fusarium chlamydosporium EtOAc extract isolated from Anvillea garcinii (Burm.f.) DC. leaves (Asteraceae). The structure elucidation and complete assignment of the isolated metabolites were performed mainly by the aid of various NMR and MS data. Fusarithioamide B (6) has been assessed for antibacterial and antifungal activities towards various microbial strains by disc diffusion assay. It exhibited selective antifungal activity towards C. albicans (MIC 1.9?µg/ml and IZD 14.5?mm), comparing to clotrimazole (MIC 2.8?µg/ml and IZD 17.9?mm). Also, it possessed high antibacterial potential towards E. coli, B. cereus, and S. aureus compared to ciprofloxacin. Furthermore, 6 was tested for the in vitro cytotoxic effect against KB, HCT-116, BT-549, MCF-7, SKOV-3, and SK-MEL cell lines. It had selective and potent effect towards BT-549, MCF-7, SKOV-3, and HCT-116 cell lines with IC₅₀s 0.09, 0.21, 1.23, and 0.59?μM, respectively compared to doxorubicin (IC₅₀s 0.046, 0.05, 0.321, and 0.24?μM, respectively). Fusarithioamide B may provide a lead molecule for future developing of antitumor and antimicrobial agents.     

Catechols from abietic acid synthesis and evaluation as bioactive compounds

Catechols from abietic acid were prepared by a short and good yielding chemical process and further evaluated for several biological activities namely, antifungal, antitumoral, antimutagenic, antiviral, antiproliferative and inhibition of nitric oxide. Their properties were compared with those of carnosic acid (6), a naturally occurring catechol with an abietane skeleton and known to possess potent antioxidant activity, as well as anticancer and antiviral properties. From all the synthetic catechols tested compound 2 showed the best activities, stronger than carnosic acid.     

Pyrrole Derivatives and Diterpene Alkaloids from the South China Sea Sponge Agelas nakamurai

Two pairs of new non‐brominated racematic pyrrole derivatives, (±)‐nakamurine D ( 1 ) and (±)‐nakamurine E ( 2 ), two new diterpene alkaloids, isoagelasine C ( 16 ) and isoagelasidine B ( 21 ), together with 13 known pyrrole derivatives ((±)‐ 3  –  15 ), five known diterpene alkaloids ( 17  –  20 , 22 ) were isolated from the South China Sea sponge Agelas nakamurai . The racemic mixtures, compounds 1  –  4 , were resolved into four pairs of enantiomers, (+)‐ 1 and (?)‐ 1 , (+)‐ 2 and (?)‐ 2 , (+)‐ 3 and (?)‐ 3 , and (+)‐ 4 and (?)‐ 4 , by chiral HPLC . The structures and absolute configurations were elucidated on the basis of comprehensive spectroscopic analyses, quantum chemical calculations, quantitative measurements of molar rotations, application of van't Hoff 's principle of optical superposition, and comparison with the literature data. The NMR and MS data of compound 3 are reported for the first time, as the structure was listed in SciFinder Scholar with no associated reference. These non‐brominated pyrrole derivatives were found in this species for the first time. Compound 18 showed valuable cytotoxicities against HL ‐60, K562, and HCT ‐116 cell lines with IC ₅₀ values of 12.4, 16.0, and 19.8 μm , respectively. Compounds 16  –  19 , 21 , and 22 showed potent antifungal activities against Candida albicans with MIC values ranging from 0.59 to 4.69 μg/ml. Compounds 16  –  19 exhibited moderate antibacterial activities against Proteusbacillus vulgaris (MIC values ranging from 9.38 to 18.75 μg/ml).     

Two new quinic acid derivatives and one new lignan glycoside from Erycibe obtusifolia

Three new compounds, 4-{erythro-2-[3-(4-hydroxyl-3-methoxyphenyl)-3-O-β-d-glucopyranosyl-propan-1-ol]}-O-medioresinol (1), (7⿳E,9⿳E,1⿳R*,3⿳S*,5⿳R*,6⿳S*)-5-O-caffeoyl-3-O-dihydrophaseicoylquinic acid (2), and (7⿳E,9⿳E,1⿳R*,3⿳S*,5⿳R*,6⿳S*)-5-O-caffeoyl-4-O-dihydrophaseicoylquinic acid (3), were isolated from Chinese folk herb Erycibe obtusifolia together with six known compounds (4⿿9). Their structures were elucidated on the basis of comparisons of literatures and extensive spectroscopic analysis, including UV, IR, HRMS, and 1D and 2D NMR techniques. Further, the cytotoxicities of these compounds were evaluated against five cell lines (HCT-8, Bel-7402, BGC-823, A549, and A2780), but they were inactive against these tumor cell lines (IC₅₀ > 10 μmol/L).     

Bioactive phenolic compounds from the Egyptian Red Sea seagrass Thalassodendron ciliatum

Five flavonoids (rutin, asebotin, 3-hydroxyasebotin, quercetin-3-O-beta-D-xylopyranoside, and a racemic mixture of catechin) and caffeic acid were isolated and identified for the first time from seagrass, Thalassodendron ciliatum, collected from the Hurghada region in Egypt. The crude extract and the isolated pure compounds were evaluated for their cytotoxic activities against HCT-116, HEPG, MCF-7, and HeLa human cancer cell lines, for their antiviral activity against Herpes Simplex and hepatitis A viruses, and for their antioxidant activity.     

Cytotoxic,antimicrobial activities,AChE and BChE inhibitory effects of compounds from Tanacetum chiliophyllum (Fisch. & Mey.) Schultz Bip. var. oligocephalum (D.C.) Sosn. and T. chiliophyllum (Fisch. & Mey.) Schultz Bip. var. monocephalum Grierson

Tanacetum L. species traditionally used for insecticidal purposes as well as in folk medicine for their antitumor, antimicrobial, antifungal activities. In our previous study a novel sesquiterpene lactone and triterpene lactone together with 12 known flavonoids, coumarin and a triterpene were isolated from T. chiliophyllum var. oligocephalum and T. chiliophyllum var. monocephalum extracts which have insecticidal and antimicrobial activity. In this study, cytotoxic, antimicrobial activities and acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory effects of pure compounds isolated from these plants were investigated. The tested compounds showed AChE and BChE inhibition which ranged between 7.20–80.37% and 9.19%–76.99% respectively. The highest AChE and BChE inhibition was observed for ulubelenolide which afforded 80.37% and 76.99% inhibition respectively. The cytotoxic effect of the compounds ranged between 22.34–49.77 μg/mL IC₅₀ values. Highest cytotoxic activity was observed against MCF-7 and HEK 293 cell line by 5–hydroxy-3′,4′,7-trimethoxy flavone and 5-hydroxy-3′,4′,6,7-tetramethoxyflavone that produced 25.80 ± 0.17 and 22.34 ± 0.70 IC₅₀ values respectively. Compounds eupatilin, cirsilineol, 5–hydroxy-3′,4′,7-trimethoxy flavone and ulubelenolide showed significant antimicrobial effect on C. albicans with 7.8 μg/mL MIC. The new compound ulubelenolide afforded high AChE and BChE inhibition as well as high antifungal activity. In our opinion activity of this substance should be evaluated further against other fungal species.     

Elucidation of the interaction of human serum albumin with anti‐cancer sipholane triterpenoid from the Red Sea sponge

A sipholane triterpenoid, named sipholenone A, with anti‐cancer properties was isolated from the Red Sea sponge Siphonochalina siphonella and characterized by proton and carbon‐13 nuclear magnetic resonance (¹H NMR and ¹³C NMR) spectroscopies. The goal of this study was to visualize the binding of this triterpenoid with human serum albumin (HSA) and to determine its binding site on the biomacromolecule. The interaction was visualized using fluorescence quenching, synchronous fluorescence, far‐ and near‐UV circular dichroism (CD), UV–visible and Fourier transform‐infrared (FT‐IR) spectroscopies. UV–visible spectroscopy indicated the formation of a ground‐state complex as a result of the interaction. Sipholenone A quenches the fluorescence of HSA via a static quenching mechanism. A small blue shift in the fluorescence quenching profiles suggested the involvement of hydrophobic forces in the interaction. Sipholenone A binding takes place at site I of subdomain II A with a 1:1 binding ratio, as revealed by displacement binding studies using warfarin, ibuprofen and digitoxin. Far‐UV CD and FT‐IR studies showed that the binding of sipholenone A to HSA also had a small effect on the protein's secondary structure with a slight decrease in the α‐helical content. Several thermodynamic parameters were calculated, along with Forster's radiative energy transfer analysis.     

Sesquiterpenes from the aerial parts of Artemisia tournefortiana

Sixteen eudesmane-type sesquiterpenes, including six unknown ones (1−6), were isolated from the aerial part of A. tournefortiana. NMR, HERIS-MS, IR spectra and ECD calculation assigned their relative and absolute configurations. Six (6, 7, 9, 13, 15, and 16) were tested for cytotoxic and anti-inflammatory activities, and seven (6, 7, 8, 12, 13, 15, and 16) were tested for antimicrobial activity. Among them, compound 15 showed significant cytotoxicity with IC₅₀ values in the range of 1.49–5.30 μM and moderate antimicrobial activity.     

Netamines O–S,Five New Tricyclic Guanidine Alkaloids from the Madagascar Sponge Biemna laboutei,and Their Antimalarial Activities

In our continuing program to isolate new compounds from the Madagascar sponge Biemna laboutei, five new tricyclic guanidine alkaloids, netamines O – S ( 1 – 5 , resp.), have been identified together with the known compounds netamine E ( 6 ) and mirabilin J ( 7 ). The structures of all new netamines were assigned on the basis of spectroscopic analyses. Their relative configurations were established by analysis of ROESY data and comparison with literature data. Netamines O, P, and Q, which were isolated in sufficient quantities, were tested for their cytotoxic activities against KB cells and their activities against the malaria parasite Plasmodium falciparum. Netamines O and Q were found to be moderately cytotoxic. Netamines O, P, and Q exhibited antiplasmodial activities with IC₅₀ values of 16.99±4.12, 32.62±3.44, and 8.37±1.35 μM , respectively.     

Exploring seascape genetics and kinship in the reef sponge Stylissa carteri in the Red Sea

A main goal of population geneticists is to study patterns of gene flow to gain a better understanding of the population structure in a given organism. To date most efforts have been focused on studying gene flow at either broad scales to identify barriers to gene flow and isolation by distance or at fine spatial scales in order to gain inferences regarding reproduction and local dispersal. Few studies have measured connectivity at multiple spatial scales and have utilized novel tools to test the influence of both environment and geography on shaping gene flow in an organism. Here a seascape genetics approach was used to gain insight regarding geographic and ecological barriers to gene flow of a common reef sponge, Stylissa carteri in the Red Sea. Furthermore, a small‐scale (<1 km) analysis was also conducted to infer reproductive potential in this organism. At the broad scale, we found that sponge connectivity is not structured by geography alone, but rather, genetic isolation in the southern Red Sea correlates strongly with environmental heterogeneity. At the scale of a 50‐m transect, spatial autocorrelation analyses and estimates of full‐siblings revealed that there is no deviation from random mating. However, at slightly larger scales (100–200 m) encompassing multiple transects at a given site, a greater proportion of full‐siblings was found within sites versus among sites in a given location suggesting that mating and/or dispersal are constrained to some extent at this spatial scale. This study adds to the growing body of literature suggesting that environmental and ecological variables play a major role in the genetic structure of marine invertebrate populations.     

Bioactive 9,11‐Secosteroids from Gorgonian Subergorgia suberosa Collected from the South China Sea

Five new 9,11‐secosteroids 1, 2 , and 4 – 6 , and seven known analogs, 3 and 7 – 12 , with the same steroid skeleton, (5αH)‐3β,6α,11‐trihydroxy‐9,11‐secocholest‐7‐en‐9‐one, were isolated from the South China Sea gorgonian Subergorgia suberosa. Among them, 2 / 3 and 4 / 5 are C(24)‐epimeric mixtures, and 6 / 7 is an (E)/(Z) mixture of (C(24)?C(28)). Their structures and relative configurations were elucidated by using comprehensive spectroscopic methods including NOESY spectra. The absolute configuration of the steroidal nucleus was established by the modified Mosher method applied to 10 and on the basis of a common biogenesis for all of these compounds. All isolated compounds, 1 – 12 , and five synthetic acetylated derivatives, 12a – 12e , were evaluated for their cytotoxicities in vitro. Compounds 4 / 5, 11, 12 , and 12b – 12d showed cytotoxic activities against K562 cell line with the IC₅₀ values ranging from 1.09 to 8.12 μM .     

Cytotoxic and haemolytic steroidal glycosides from the Caribbean sponge Pandaros acanthifolium

Six new steroidal saponins, pandarosides K–M (1–3) and their methyl esters (4–6), were isolated as minor components, after a careful chemical reinvestigation of the Caribbean sponge Pandaros acanthifolium. Their structures were established on the basis of spectroscopic analyses and comparison with the data obtained from previous metabolites of this family. All new compounds showed moderate to weak activity against four parasitic protozoa. Additionally, these compounds and previously reported pandarosides and acanthifoliosides were tested on three human tumour cell lines, and their haemolytic and liposome permeabilizing activity were assessed. Two pandarosides exhibited moderate to strong cytotoxic effect, while three acanthifoliosides showed strong haemolytic activity.     

A new cerebroside and bioactive compounds from Celtis adolphi-friderici Engl. (Cannabaceae)

A phytochemical investigation of the roots of Celtis adolphi-friderici Engl. led to the isolation of a previously undescribed cerebroside named, eloundemnoside (1), alongside with seventeen known compounds (2–18). Their chemical structures were elucidated based on the analysis of their NMR and MS data. All the compounds were isolated from this specie for the first time, while eight known compounds (4–5, 12–13, 15–18) are obtained from the genus Celtis for the first time. The isolates were screened for their antioxidant, lipoxygenase, urease, and butyrylcholinesterase enzyme inhibitory activities. Compounds 4, 7 and 12 showed good antioxidant activities with IC₅₀ values of 22.2, 29.3, and 13.2 μM, respectively. In addition, azelaic acid (12) showed the best lipoxygenase inhibition (IC₅₀ value of 16.3 μM), while friedelin (2) exhibited the highest inhibition of urease with an IC₅₀ value of 15.3 μM. However, all the compounds tested had moderate butyrylcholinesterase inhibitory properties. The chemophenetic relationship of the isolates and their significance were discussed.     

New bioactive dihydrofuranocoumarins from the roots of the Tunisian Ferula lutea (Poir.) Maire

A phytochemical investigation of the roots of Ferula lutea (Poir.) Maire led to the isolation of new dihydrofuranocoumarins as two inseparable isomers, (?)-5-hydroxyprantschimgin 1 and (?)-5-hydroxydeltoin 2, together with eight known compounds, (?)-prantschimgin 3, (?)-deltoin 4, psoralen 5, xanthotoxin 6, umbelliferone 7, caffeic acid 8, β-sitosterol 9 and stigmasterol 10. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D and 2D NMR experiments and mass spectroscopy analysis, as well as by comparison with literature data. The anti-acetylcholinesterase and cytotoxic effects of the isolates and antioxidant activities of the mixture (1+2) were also evaluated in this work. Results showed that the mixture (1+2) has the most cytotoxic activity with IC₅₀ values 0.29 ± 0.05 and 1.61 ± 0.57 μM against the cell lines HT-29 and HCT 116, respectively. The greatest acetylcholinesterase inhibitory activity (IC₅₀ = 0.76 ± 0.03) was exhibited by the xanthotoxin 6. In addition, the mixture (1+2) was investigated for its antioxidant activity and showed IC₅₀ values 18.56, 13.06, 7.59, and 4.81 μM towards DPPH free radical scavenging, ABTS radical monocation, singlet oxygen and hydrogen peroxide, respectively.