Cytotoxic bibenzyls, and germacrane- and pinguisane-type sesquiterpenoids from Indonesian, Tahitian and Japanese liverworts

Cytotoxic bibenzyls, and germacrane- and pinguisane-type sesquiterpenoids have been isolated from unidentified Indonesian and Tahitian Frullania sp. and Japanese Porella perrottetiana by using a combination of chromatographic methods. The structure activity relationship (SAR) study showed that the presence of a phthalide group in bibenzyls, an alpha-methylene-gamma-lactone in germacrane-type sesquiterpenoids, and beta-hydroxycarbonyl in pinguisane-type sesquiterpenoids play an important role in providing cytotoxic activity against both human promyelocytic leukemia (HL-60) and human pharyngeal squamous carcinoma (KB) cell lines. The structure of each isolated compound was elucidated by using spectroscopic methods and the cytotoxicity was determined by using the WST-8 colorimetric assay.     

Chemical constituents of Malagasy liverworts, part II: mastigophoric acid methyl ester of biogenetic interest from Mastigophora diclados (Lepicoleaceae Subf. Mastigophoroideae)

In the course of our chemotaxonomic study of the liverworts growing in Madagascar, mastigophoric acid methyl ester, along with eleven known compounds were isolated from Mastigophora diclados. Isolated metabolites showed that the Malagasy Mastigophora is more related to the samples from Borneo and Japan than to the Taiwanese or Malaysian ones. The biosynthesis of the herbertane type sesquiterpenoids from Mastigophora diclados is suggested to be similar to those found in the genus Herbertus. The herbertane-type sesquiterpenoids were screened for Staphylococcus aureus strain inhibition.     

Phytochemical analysis and antimicrobial activities of methanolic extracts of leaf, stem and root from different varieties of Labisa pumila Benth

A local herb, Kacip Fatimah, is famous amongst Malay women for its uses in parturition; however, its phytochemical contents have not been fully documented. Therefore, a study was performed to evaluate the phenolics, flavonoids, and total saponin contents, and antibacterial and antifungal properties of the leaf, stem and root of three varieties of Labisia pumila Benth. Total saponins were found to be higher in the leaves of all three varieties, compared to the roots and stems. Leaves of var. pumila exhibited significantly higher total saponin content than var. alata and lanceolata, with values of 56.4, 43.6 and 42.3 mg diosgenin equivalent/g dry weight, respectively. HPLC analyses of phenolics and flavonoids in all three varieties revealed the presence of gallic acid, caffeic acid, rutin, and myricetin in all plant parts. Higher levels of flavonoids (rutin, quercitin, kaempferol) were observed in var. pumila compared with alata and lanceolata, whereas higher accumulation of phenolics (gallic acid, pyrogallol) was recorded in var. alata, followed by pumila and lanceolata. Antibacterial activities of leaf, stem and root extracts of all varieties determined against both Gram positive (Micrococcus luteus, Bacillus subtilis B145, Bacillus cereus B43, Staphylococcus aureus S1431) and Gram negative (Enterobacter aerogenes, Klebsiella pneumonia K36, Escherichia coli E256, Pseudomonas aeruginosa PI96) pathogens showed that crude methanolic extracts are active against these bacteria at low concentrations, albeit with lower antibacterial activity compared to kanamycin used as the control. Antifungal activity of methanolic extracts of all plant parts against Fusarium sp., Candida sp. and Mucor using the agar diffusion disc exhibited moderate to appreciable antifungal activities compared to streptomycin used as positive control.     

Chemical constituents of the fermentative extracts of marine fungi Phoma sp. CZD-F11 and Aspergillus sp. CZD-F18 from Zhoushan Archipelago,China

A new diphenyl ether (1) as well as 20 other compounds were identified from the fermentative extracts of marine-derived fungi Phoma sp. CZD-F11 (Compounds 1–8) and Aspergillus sp. CZD-F18(Compounds 9–21). Their structures were elucidated on the basis of extensive spectroscopic analysis. The broth extracts of the fungi exhibited very good anticancer activity against H1975 cells with 5.62 and 25.8% viability at concentration of 10 μg/mL for Phoma sp. CZD-F11 and Aspergillus sp. CZD-F18, respectively. The inhibitory activity of all compounds against PC-3 cell lines, BRD4 and aromatase were evaluated. The results showed compound 7 exhibited moderate anticancer activity with 66.1% inhibition against PC-3 cell lines at the concentration of 10 μg/mL. Compound 7 and 8 exhibited favourable BRD4 inhibitory activity with 78.5 and 76.4% inhibition at the concentration of 10 μg/mL.     

Lecythomycin, a new macrolactone glycoside from the endophytic fungus Lecythophora sp

A new macrolactone glycoside, lecythomycin (1), 23-methyl-3-(1-O-mannosyl)-oxacyclotetracosan-1-one, was isolated from the endophytic fungus Lecythophora sp. (code 30.1), an endopyte of the Indonesian plant Alyxia reinwardtii. The structure of 1 was elucidated on the basis of NMR spectroscopic and mass spectrometric data. The isolated compound displayed antifungal activity against strains of Aspergillus fumigatus and Candida kruzei at minimal inhibitory concentrations (MIC) of 62.5-125 microg/mL.     

Antiprotozoal, antitubercular and cytotoxic potential of cyanobacterial (blue-green algal) extracts from Ireland

Cyanobacteria (= blue-green algae) are prolific producers of structurally distinct and biologically active metabolites. In the continuation of our search for new sources of anti-infective natural products, we have assessed the in vitro antiprotozoal (Plasmodium falciparum, Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani) and antitubercular (Mycobacterium tuberculosis) potential of samples of two terrestrial cyanobacteria, Nostoc commune (collected when desiccated and wet) and Rivularia biasolettiana. The cytotoxic potential of the extracts was also evaluated against primary L6 cells. Except for T. cruzi and M. tuberculosis, the crude extracts were active against all the organisms tested and showed no toxicity. The crude extracts were then partitioned between n-hexane, chloroform and aqueous methanol and retested against the same panel of pathogens. The chloroform sub-extracts of both N. commune samples showed significant activity against T. b. rhodesiense (IC50 values 2.0 and 3.5 microg/mL) and P. falciparum (IC50s 7.4 and 5.8 microg/mL), with low toxicity. This trend was also true for R. biasolettiana extracts, and its chloroform sub-extract showed notable activity against all parasitic protozoa. There were differences in the biological activity profiles of extracts derived from desiccated and hydrated forms of N. commune. To our knowledge, this is the first study assessing the anti-infective activity of desiccated and hydrated forms of N. commune, as well as R. biasolettiana. Furthermore, the present work reports such biological activity in terrestrial cyanobacteria from Ireland for the first time. These results warrant the further study of Irish terrestrial cyanobacteria as a valuable source of new natural product leads for the treatment of parasitic protozoal infections.     

Indonesian propolis: chemical composition, biological activity and botanical origin

From a biologically active extract of Indonesian propolis from East Java, 11 compounds were isolated and identified: four alk(en)ylresorcinols (obtained as an inseparable mixture) (1-4) were isolated for the first time from propolis, along with four prenylflavanones (6-9) and three cycloartane-type triterpenes (5, 10 and 11). The structures of the components were elucidated based on their spectral properties. All prenylflavanones demonstrated significant radical scavenging activity against diphenylpicrylhydrazyl radicals, and compound 6 showed significant antibacterial activity against Staphylococcus aureus. For the first time Macaranga tanarius L. and Mangifera indica L. are shown as plant sources of Indonesian propolis.     

Xenimanadins A-D, a family of xenicane diterpenoids from the Indonesian soft coral Xenia sp.

Four novel xenicane diterpenoids, xenimanadins A-D (1-4), characterized by the unusual 2,6-dimethoxytetrahydropyran functionality, have been isolated from the Indonesian soft coral Xenia sp., together with three known xeniolides. The stereostructure of these metabolites has been established through extensive interpretation of NMR data and application of the modified Mosher method. Xenimanadins were tested against tumor cell lines, revealing details about the cytotoxic potential of xenicane diterpenoids.     

Polarity Directed Appraisal of Pharmacological Potential and HPLC-DAD Based Phytochemical Profiling of Polygonum glabrum Willd

The present study was designed to evaluate polarity-dependent extraction efficiency and pharmacological profiling of Polygonum glabrum Willd. Crude extracts of leaves, roots, stems, and seeds, prepared from solvents of varying polarities, were subjected to phytochemical, antioxidant, antibacterial, antifungal, antidiabetic, and cytotoxicity assays. Maximum extraction yield (20.0% w/w) was observed in the case of an acetone:methanol (AC:M) root extract. Distilled water:methanol (W:M) leaves extract showed maximum phenolic contents. Maximum flavonoid content and free radical scavenging potential were found in methanolic (M) seed extract. HPLC-DAD quantification displayed the manifestation of substantial quantities of quercetin, rutin, gallic acid, quercetin, catechin, and kaempferol in various extracts. The highest ascorbic acid equivalent total antioxidant capacity and reducing power potential was found in distilled water roots and W:M leaf extracts, respectively. Chloroform (C) seeds extract produced a maximum zone of inhibition against Salmonella typhimurium. Promising protein kinase inhibition and antifungal activity against Mucor sp. were demonstrated by C leaf extract. AC:M leaves extract exhibited significant cytotoxic capability against brine shrimp larvae and α-amylase inhibition. Present results suggest that the nature of pharmacological responses depends upon the polarity of extraction solvents and parts of the plant used. P. glabrum can be considered as a potential candidate for the isolation of bioactive compounds with profound therapeutic importance.     

Antibacterial activity of eight Brazilian annonaceae plants

Sixteen extracts, obtained from eight Brazilian plants of Annonaceae family, were screened for their antibacterial activity: Xylopia frutescens, X. aromatica, X. amazonica, X. benthamii, Annona ambotay, A. crassiflora, A. muricata and A. cherimolia. Amongst the investigated extracts, six showed antibacterial activity against at least one of the tested organisms at the concentration of 100 microg/mL. The most active extracts were those prepared from X. frutescens, X. amazonica, and A. ambotay. A phytochemical screening showed the presence of anonaceus acetogenins in some active extracts. Eleven diterpenoids were also tested for comparison purposes. Six were natural products, previously isolated from Xylopia sp. (kaurenoic, frutoic, xylopic, 15beta-hydroxy-kaurenoic and trachylobanic acids plus kaurenol) and five were derivatives of such compounds, obtained by esterification or reduction reactions. Trachylobanic acid showed antibacterial activity against B. subtilis and S. aureus.     

Sceliphrolactam, a polyene macrocyclic lactam from a wasp-associated Streptomyces sp

A previously unreported 26-membered polyene macrocyclic lactam, sceliphrolactam, was isolated from an actinomycete, Streptomyces sp., associated with the mud dauber, Sceliphron caementarium. Sceliphrolactam's structure was determined by 1D- and 2D-NMR, MS, UV, and IR spectral analysis. Sceliphrolactam displays antifungal activity against amphotericin B-resistant Candida albicans (MIC = 4 μg/mL, 8.3 μM).     

Chemical diversity and anti-proliferative activity of marine algae

The chemical diversity of three macroalgae (Ulva reticulata, Sargassum wightii, Gracilaria sp) were determined using the GC-MS method with principal component analysis (PCA) and their potential efficacy against human pathogens and cervical carcinoma cells evaluated using MTT bioassay method. Our results showed that >30 metabolites were detected in three seaweeds, among these, steroids and fatty acids are the most dominant chemical group that highly contributes to discriminate this species. The PCA of GC-MS mass spectral variables showed a clear discrimination between three different species based on the phytochemical diversity of seaweeds. The extracts of U. reticulata exhibited anti-microbial activity with Pseudomonas aeruginosa (6.00?mm) and showed potential anti-proliferative activity against the HeLa cells (IC₅₀ 37?µmol/L) at concentration 1–50?µM treatment. Results of this study concluded that PCA analysis of mass spectral variables could be utilized as a reliable tool for species discrimination and chemotaxonomic classification of seaweeds.     

Phytochemical Characterization and Bioactivity of Asparagus acutifolius: A Focus on Antioxidant,Cytotoxic, Lipase Inhibitory and Antimicrobial Activities

The phytochemical composition of leaves, stems, pericarps and rhizomes ethanolic extracts of Asparagus acutifolius were characterized by HPLC-DAD-MS. A. acutifolius samples contain at least eleven simple phenolics, one flavonon, two flavonols and six steroidal saponins. The stem extracts showed the highest total phenolic acid and flavonoid contents, where cafeic acid and rutin were the main compounds. No flavonoids were detected in the leaf, pericarp or rhizome while caffeic acid and ferulic acid were the predominant. Steroidal saponins were detected in the different plant parts of A. acutifolius, and the highest contents were found in the rhizome extracts. The stem extracts exhibited the highest antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) and the highest 2,2-azino-bis (3 ethylbenzothiazoline-6-sulphonic acid) (ABTS) scavenging activity was found in the pericarp extracts. The rhizome and leaf extracts showed a potent cytotoxic activity against HCT-116 and HepG2 cell lines. Moreover, the pericarp and rhizome extracts revealed a moderate lipase inhibitory activity. The leaf and rhizome extracts were screened for their antimicrobial activity against human pathogenic isolates. The leaf extract exhibited a powerful inhibitory activity against all the bacteria and fungi tested.     

Oxygenated cembranoids of the decaryiol type from the Indonesian soft coral Lobophytum sp.

Three novel cembrane diterpenoids, decaryiols B-D (5-7), characterized by a bicyclic skeleton of the decaryiol-type, have been isolated from the Indonesian soft coral Lobophytum sp., along with three known cembranoids. The stereostructures of these metabolites have been established through extensive NMR spectroscopic analysis, application of the modified Mosher method, and chemical conversion. Cembranoids obtained from Lobophytum sp. (2-7) and six semisynthetic derivatives (9-14) prepared from decaryiol were tested for cell growth inhibitory activity against three different cell lines. O-Methyl decaryiol (10) exhibited a significant and selective activity against glioma cell lines.     

Cladieunicellins A-E, new eunicellins from an Indonesian soft coral Cladiella sp

Five new eunicellin-type diterpenoids, cladieunicellins A-E (1-5), were isolated from an Indonesian soft coral identified as Cladiella sp. The structures of diterpenoids 1-5 were established using spectroscopic methods. Eunicellins 2 and 5 were found to be cytotoxic against DLD-1 and HL-60 tumor cells, respectively, and 3 displayed inhibitory effects against superoxide anion generation by human neutrophils.     

Phytochemical Profile and Anticancer Potential of Endophytic Microorganisms from Liverwort Species,Marchantia polymorpha L.

Liverwort endophytes could be a source of new biologically active substances, especially when these spore-forming plants are known to produce compounds that are not found in other living organisms. Despite the significant development of plant endophytes research, there are only a few studies describing liverwort endophytic microorganisms and their metabolites. In the presented study, the analysis of the volatile compounds obtained from thallose liverwort species, Marchantia polymorpha L., and its endophytes was carried out. For this purpose, non-polar extracts of plant material and symbiotic microorganisms were obtained. The extracts were analyzed using gas chromatography coupled to mass spectrometry. Compounds with the structure of diketopiperazine in the endophyte extract were identified. Liverwort volatile extract was a rich source of cuparane-, chamigrane-, acorane-, and thujopsane-type sesquiterpenoids. The cytotoxicity of ethyl acetate extracts from endophytic microorganisms was evaluated on a panel of cancer (FaDu, HeLa, and SCC-25) cell lines and normal (VERO), and revealed significant anticancer potential towards hypopharyngeal squamous cell carcinoma and cervical adenocarcinoma.     

Antioxidant, antitubercular and cytotoxic activities of Piper imperiale

Phenolic compounds are widely distributed in Nature and act as pharmacologically active constituents in many herbal medicines. They have multiple biological properties, most notably antioxidant, antibacterial and cytotoxic activities. In the present study an attempt to correlate the phenolic composition of leaf, flower and wood extracts of Piper imperiale, with antioxidant, antitubercular and cytotoxic activities was undertaken. The total phenol content ranged from 1.98 to 6.94 mg GAE/gDW among ethanolic extracts, and gallic acid, catechin, epicatechin, ferulic acid, resveratrol and quercetin were identified and quantified by HPLC. DPPH and ABTS assays showed high antioxidant activity of the leaf extract (EC(50ABTS) = 15.6 μg/mL, EC(50DPPH) = 27.3 μg/mL) with EC?? in the same order of magnitude as the hydroxyquinone (EC(50ABTS) = 10.2 μg/mL, EC(50DPPH) = 15.7 μg/mL). The flower extract showed strong antimicrobial activity against Mycobacterium tuberculosis H??Rv. All the extracts exhibited dose-dependent cytotoxic effects against MCF-7 cancer cells. This is the first time that a Piper extract has been found to be highly active against M. tuberculosis. This study shows the biological potential of Piper imperiale extracts and gives way to bio-guided studies with well-defined biological activities.     

Studies on differentiation-inducing activities of triterpenes.

Differentiation-inducing activity of over 180 extracts of crude drugs and plants was tested using mouse myeloid leukemia cell line (M1). The methanol extracts of clove (Syzygium aromaticum Merrill et Perry, Myrtaceae) showed remarkable induction of differentiation of M1 cells into macrophage-like cells. From the extract, oleanolic acid (1) and crategolic acid (2) were isolated as the active components. We also tested other triterpenes, such as oleananes, ursanes and dammaranes, to investigate the structure-activity relationship. Some triterpene aglycones showed differentiation-inducing activity, but triterpene glycosides showed little activity. Furthermore, the differentiation-inducing activity of these triterpene compounds was tested against human acute promyelocytic leukemia cell line (HL-60).     

Kinase inhibitory, haemolytic and cytotoxic activity of three deep-water sponges from North Western Australia and their fatty acid composition

The c-AMP dependent protein kinase (PKA) inhibition, haemolytic activity, and cytoxicity of 21 extracts obtained from North Western Australian sponges collected from depths of 84-135 m were investigated. Hexane extracts from Ircinia/Sarcotragus sp. and Geodia sp. displayed PKA inhibitory activities of 100 and 97% respectively (at 100 microg/mL), while aq. methanol extracts from Haliclona sp. exhibited potent haemolytic activity (75%) and hexane extracts from Geodia sp. were highly toxic (88%) to the brine shrimp Artemia franciscana. As the non-polar extracts gave the greatest PKA inhibition, these were further analysed by GC-MS and 29 fatty acids were identified in the highest proportions in Ircinia/Sarcotragus sp. > Haliclona sp. > Geodia sp. In contrast to shallow-water sponges that are dominated by polyunsaturated fatty acids with a high percentage of long chain fatty acids, LCFAs (C24-C30), the deep-sea sponges investigated herein were all found to be rich in saturated fatty acids, in particular C14-C20 fatty acids, including odd and branched chain fatty acids, with only low levels (0-10%) of LCFAs. Screening of the PKA inhibitory activity of a series of commercially available fatty acids identified C14-C18 fatty acids as possessing significant PKA inhibitory activity that may contribute to the activity observed in the sponges studied.     

Antifungal Activity of Chemical Constituents from Piper pesaresanum C. DC. and Derivatives against Phytopathogen Fungi of Cocoa

In this study, the antifungal potential of chemical constituents from Piper pesaresanum and some synthesized derivatives was determined against three phytopathogenic fungi associated with the cocoa crop. The methodology included the phytochemical study on the aerial part of P. pesaresanum, the synthesis of some derivatives and the evaluation of the antifungal activity against the fungi Moniliophthora roreri, Fusarium solani and Phytophthora sp. The chemical study allowed the isolation of three benzoic acid derivatives (1–3), one dihydrochalcone (4) and a mixture of sterols (5–7). Seven derivatives (8–14) were synthesized from the main constituents, of which compounds 9, 10, 12 and 14 are reported for the first time. Benzoic acid derivatives showed strong antifungal activity against M. roreri, of which 11 (3.0 ± 0.8 µM) was the most active compound with an IC₅₀ lower compared with positive control Mancozeb^® (4.9 ± 0.4 µM). Dihydrochalcones and acid derivatives were active against F. solani and Phytophthora sp., of which 3 (32.5 ± 3.3 µM) and 4 (26.7 ± 5.3 µM) were the most active compounds, respectively. The preliminary structure–activity relationship allowed us to establish that prenylated chains and the carboxyl group are important in the antifungal activity of benzoic acid derivatives. Likewise, a positive influence of the carbonyl group on the antifungal activity for dihydrochalcones was deduced.