Bioactive 2-pyrone metabolites from an endophytic Phomopsis asparagi SWUKJ5.2020 of Kadsura angustifolia

Five new 2-pyrone metabolites, phomaspyrones A–E (1–5) along with three known compounds, macommelin-8,9-diol (6), macommelin-9-ol (7), and macommelin (8), were isolated from the culture broth of an endophytic fungus Phomopsis asparagi SWUKJ5.2020 of medicinal plant Kadsura angustifolia by sequentially purification over silica gel, Sephadex LH-20 column chromatography and preparative HPLC. Their structures were elucidated on the basis of spectroscopic analysis, including two-dimensional (2D) NMR and HRMS (ESI-TOF) data. Among them, compounds 3–5 exhibited notable cytotoxicity against HL-60 and K562 cells with IC₅₀ values of below 10 μg/mL better than those of the other isolated metabolites (IC₅₀ = 10.6–26.6 μg/mL). The results showed that the keto or hemiketal functionality might play an important role in cytotoxic activity of this class of compounds.     

Chemical constituents from Ainsliaea acerifolia as potential anti-obesity agents

Bioassay-guided isolation of an ethanolic extract of the aerial parts from Ainsliaea acerifolia using pancreatic lipase inhibitory assay led to the isolation of a new guaianolide-type sesquiterpene lactone (1), a new dicaffeoylquinic acid derivative (4), as well as eight known secondary metabolites. Structures of the two new compounds were elucidated on the basis of spectroscopic methods. All isolated compounds were evaluated for their inhibitory effects against pancreatic lipase, and compound 2 exhibited significant inhibitory activity with an IC₅₀ value of 15.3 ± 0.7 μM. Furthermore, compound 2 also exhibited potent inhibitory effects against 3T3-L1 adipocyte cells.     

Lemairones A and B: Two new antibacterial tetraflavonoids from the leaves of Zanthoxylum lemairei (Rutaceae)

Zanthoxylum lemairei is widely used in African folk medicine for its pharmacological relevance. Chemical investigation of the ethanol extract from the leaves of this plant lead to the isolation of two new tetraflavonoids, lemairones A (1) and B (2), along with three known compounds, lupeol, sitosterol, and sitosterol 3-O-β-d-glucopyranoside. The antibacterial screening of the leaves of this plant, characterization of compounds 1 and 2, and their antibacterial activity are reported for the first time. The isolation of the compounds was performed using different chromatographic methods while their structures were elucidated by spectroscopic techniques including MS and NMR, and by comparison of data with those of similar flavonoids reported in the literature. The isolated compounds and the crude extract were tested against ten Gram negative multi-resistance bacterial strains including clinical isolates using a broth dilution method. The crude ethanol extract showed weak activity against the tested bacteria strains with a minimal inhibitory concentration (MIC) ranging from 512 to 1024 μg/mL. Among the isolated metabolites, only the new tetraflavonoids were tested. Lemairone A displayed weak activity while lemairone B had moderate activity against the resistant Escherichia coli AG100 with MIC values of 128 μg/mL and 64 μg/mL respectively. In addition, both molecules displayed weak activity against Klebsiella pneumoniae KP55 (MIC 128 μg/mL).     

Depsidones from Talaromyces stipitatus SK-4, an endophytic fungus of the mangrove plant Acanthus ilicifolius

An endophytic fungus (Talaromyces stipitatus SK-4) was isolated from the leaves of a mangrove plant Acanthus ilicifolius. Its crude extract exhibited significant antibacterial activity and was purified to afford two new depsidones, talaromyones A and B (1 and 2), along with five known depsidone analogs (3–7). Their structures, including absolute configuration, were elucidated through extensive spectroscopic data analysis and modified Mosher's method. Compound 2 showed antibacterial activity against Bacillus subtilis with an MIC value of 12.5 μg/mL. In the inhibitory assay against α-glucosidase, compounds 2, 4 and 5 displayed moderate activities with IC₅₀ values ranging from 48.4 to 99.8 μM.     

Tyroscherin and tyroscherin analogs from Pseudallescheria boydii SNB-CN85 isolated from termite Termes cf. hispaniolae

Two new tyroscherin derivatives: N-methyl-tyroscherone (2) and tyroscherin N,O-acetonide (3), as well as two known secondary metabolites tyroscherin (1) and pseurotin A (4), were isolated from a solid culture of the termite-borne fungus Pseudallescheria boydii SNB-CN85. The structures were elucidated by spectroscopic analysis and chemical modification. Compound 3 was synthesized from tyroscherin (1) in the free amine form by heating in deuterated acetone, followed by deuterium-proton exchange in MeOH. All compounds were tested for their antimicrobial activities on C. albicans and S. aureus, and 2 and 3 exhibited minimal inhibitory concentrations between 128 and 8 μg mL⁻¹.     

New pyranonaphthazarin and 2-naphthoic acid derivatives from the mangrove endophytic fungus Leptosphaerulina sp. SKS032

Two new compounds, named leptospyranonaphthazarin A (1) and leptosnaphthoic acid A (2), together with four known compounds (3–6) were isolated from an endophytic fungus Leptosphaerulina sp. SKS032. Their structures were assigned using spectroscopic methods, computational methods, and single-crystal X-ray diffraction analysis. In the antibiotic assay, compounds 1, 2, and 6 exhibited antibacterial activities against Staphylococcus aureus with minimal inhibitory concentration (MIC) values of 25.0, 50.0, and 50.0 μg/mL, respectively.     

Ellagitannin and flavonoid constituents from Agrimonia pilosa Ledeb. with their protein tyrosine phosphatase and acetylcholinesterase inhibitory activities

A new ellagitannin, agritannin (1), a new flavone glycoside, agriflavone (2), and another flavone glycoside with spectroscopic data reported for the first time, kaempferol-3-O-[(S)-3-hydroxy-3-methylglutaryl (1→6)]-β-d-glucoside (3), along with 16 known compounds were isolated from the aerial parts of Agrimonia pilosa Ledeb. These compounds were evaluated for PTP1B inhibitory activity. Among them, compounds 9 and 18 displayed potential inhibitory activity against PTP1B with IC₅₀ values of 7.14 ± 1.75 and 7.73 ± 0.24 μM, respectively. In addition, compound 1 showed significant inhibitory effect with an IC₅₀ value of 17.03 ± 0.09 μM. Furthermore, these compounds were tested in AChE inhibitory assays. Most of them were found to have moderate inhibitory effects, with IC₅₀ values ranging from 60.20 ± 1.09 to 92.85 ± 1.12 μM. Except compounds 3, 8, and 18 were inactive.     

Protein tyrosine phosphatase 1B inhibitory effects of depsidone and pseudodepsidone metabolites from the Antarctic lichen Stereocaulon alpinum

Seven phenolic lichen metabolites (1–7) have been isolated from a methanol extract of the Antarctic lichen Stereocaulon alpinum by various chromatographic methods. The structures of these compounds were determined mainly by analysis of NMR spectroscopic data. A depsidone-type compound, lobaric acid (1) and two pseudodepsidone-type compounds, 2 and 3, exhibited potent inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC₅₀ values of 0.87 μM, 6.86 μM, and 2.48 μM, respectively. Kinetic analyses of PTP1B inhibition by compounds 1 and 2 suggested that these compounds inhibited PTP1B activity in a non-competitive manner.     

Aspernolides F and G,new butyrolactones from the endophytic fungus Aspergillus terreus

Two new butyrolactones: aspernolides F (6) and G (7), together with three stigmasterol derivatives: (22E,24R)-stigmasta-5,7,22-trien-3-β-ol (1), stigmast-4-ene-3-one (2), and stigmasta-4,6,8(14), 22-tetraen-3-one (3), two meroterpenoids: terretonin A (4) and terretonin (5), and a butyrolactone derivative: butyrolactone VI (8) have been isolated from the endophytic fungus Aspergillus terreus isolated from the roots of Carthamus lanatus (Asteraceae). Their structures were determined by spectroscopic means (1D, 2D NMR, and HRESIMS), as well as optical rotation measurement and comparison with literature data. The isolated compounds were evaluated for their anti-microbial, anti-malarial, anti-leishmanial, and cytotoxic activities. Compound 1 displayed a potent activity against MRSA and C. neoformans with IC₅₀ values of 0.96 μg/mL and 4.38 μg/mL, respectively compared to ciprofloxacin (IC₅₀ 0.07 μg/mL) and amphotericin B (IC₅₀ 0.34 μg/mL), respectively. While, 6 showed good activity against C. neoformans (IC₅₀ 5.19 μg/mL) and mild activity against MRSA (IC₅₀ 6.39 μg/mL). Moreover, 1 and 2 exhibited very good anti-leishmanial activity towards L. donovani with IC₅₀ values of 4.61 and 6.31 μg/mL, respectively and IC₉₀ values of 6.02 and 16.71 μg/mL, respectively.     

Acetylcholinesterase inhibitory activity and mutagenic effects of Croton penduliflorus leaf extract constituents

Croton penduliflorus is a medicinal plant widely employed in the management of inflammatory conditions, infections and oxidative stress related diseases. The activities demonstrated by leaf extracts indicate that they possess the ability to reduce oxidative damage to cells. Repeated column fractionation of the ethyl acetate fraction of a 20% aqueous methanol leaf extract of C. penduliflorus on Sephadex LH-20 afforded four phenolic compounds: quercetin-3-O-rhamnoside (1), kaempferol-3-O-rhamnoside (2), protocatechualdehyde (3A) and its solvent derived dimer (3B) along with p-hydroxybenzoic acid (4). Compound 3B is described for the first time and its significance in bioassay is briefly outlined. Structure elucidation of the isolated compounds was carried out using spectroscopic techniques. The inhibitory properties of the four compounds against acetylcholinesterase were determined using the microplate assay. The IC₅₀ values of the isolated compounds ranged from 87.9 to 1231.9 μM, with compound 2 having the best inhibitory activity (IC₅₀ = 87.9 μM). The four isolated compounds showed no mutagenic effects against Salmonella typhimurium tester strains TA98 and TA100. The moderate activity demonstrated by these compounds suggests that they could be helpful in the management of neurodegenerative disorders.     

Pentacyclic hemiacetal sterol with antifouling and cytotoxic activities from the soft coral Nephthea sp.

A novel unusual pentacyclic hemiacetal sterol nephthoacetal (1), was isolated from soft coral Nephthea sp. The structure of this sterol was inferred from its two acetyl derivatives (2) and (3), by means of spectroscopic methods, and quantum chemical calculations. Anti-fouling activity of compounds 1–3 against Bugula neritina larvae was evaluated, sterol (1) exhibited significant inhibitory effect with EC₅₀ value of 2.5 μg/mL, while having low toxicity with LC₅₀ >25.0 μg/mL. The in vitro cytotoxic activity of compounds 1–3 against HeLa cells was also evaluated, all of them exhibited moderate cytotoxicity with IC₅₀ values of 12.3 (1), 10.1 (2), and 19.6 μg/mL (3), respectively.     

Three new geranyl aurones from the leaves of Artocarpus altilis

From the MeOH extract of the leaves of Artocarpus altilis (Moraceae), three new aurones, altilisin H (1), I (2), and J (3), have been isolated together with two known flavonoids. Their structures were elucidated on the basis of spectroscopic data. All compounds possessed tyrosinase inhibitory activity with IC₅₀ values less than 100 μM, while compounds 1–3 displayed potent α-glucosidase inhibitory activity with IC₅₀ values ranging from 4.9 to 5.4 μM.     

3-Anhydro-6-hydroxy-ophiobolin A,a new sesterterpene inhibiting the growth of methicillin-resistant Staphylococcus aureus and inducing the cell death by apoptosis on K562, from the phytopathogenic fungus Bipolaris oryzae

A new ophiobolin derivative, 3-anhydro-6-hydroxy-ophiobolin A (1), as well as two known ophiobolin derivatives 3-anhydro-ophiobolin A (2) and 3-anhydro-6-epi-ophiobolin A (3) were isolated from the PDB culture of a phytopathogenic fungus Bipolaris oryzae. The structure of 1 was elucidated through 2D NMR and other spectroscopic techniques. Compound 1 exhibited strong antimicrobial activity against Bacille Calmette–Guerin, Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus with MIC value of 12.5 μg/mL, and potent antiproliferative activity against cell lines HepG2 and K562 with IC₅₀ of 6.49 μM and 4.06 μM, respectively. Further studies on the cytotoxicity of compound 1 against K562 cells demonstrated that it induced apoptosis, observed by flow cytometric method. Preliminary structure–activity relationships of these ophiobolins and the mechanism of apoptosis induced by 1 were analyzed.     

Cytotoxic naphthoquinone and a new succinate ester from the soil fungus Fusarium solani PSU-RSPG227

A new naphthoquinone, solaninaphthoquione (1), and a new succinate ester derivative, 4-(4-hydroxyphenethoxy)-4-oxobutanoic acid (2), were isolated from the soil fungus Fusarium solani PSU-RSPG227 together with five previously reported compounds; javanicin (3), monaspilosin (4), aspergillol B (5), tyrosol (6) and 4-hydroxyphenylacetic acid (7). Their structures were elucidated primarily by NMR spectroscopic data. Due to paucity of materials, compounds 2, 4 and 5 as well as analogues of 5 were prepared for biological activity evaluation. Compound 1 showed significant cytotoxic activity against breast cancer (MCF-7) cells and mild cytotoxic activity against oral human carcinoma (KB) cells (IC₅₀ values of 21.3 and 22.6 μM, respectively) compared to standard compounds. Compound 1 also displayed weak antimalarial activity (IC₅₀ of 26.1 μM).     

A novel sesquiterpene quinone from Hainan sponge Dysidea villosa

A new sesquiterpene quinone, 21-dehydroxybolinaquinone (5), together with two known related analogues, bolinaquinone (6) and dysidine (7), had been isolated from the Hainan sponge Dysidea villosa. The structure of the new compound 5 was elucidated on the basis of detailed analysis of spectroscopic data and by comparison with related model compounds. Compounds 5–7 were evaluated for the inhibitory activity against hPTP1B, a potential drug target for treatment of type-II diabetes and obesity, and cytotoxic activity against Hela cell line. The results showed that dysidine (7) had the strongest hPTP1B inhibitory activity with an IC₅₀ value of 6.70 μM and 6 had significant cytotoxic activity against Hela cell line with an IC₅₀ value of 5.45 μM. New compound 5 showed moderate PTP1B inhibitory activity and cytotoxicity with IC₅₀ values of 39.50 and 19.45 μM, respectively.     

Four new sesquiterpenoids as natural nitric oxide (NO) inhibitors from the rhizomes of Curcuma phaeocaulis

A new norsesquiterpene named phaeocaulisin N (1), and three new guaiane-type sesquiterpenes named phaeocaulisins O–Q (2–4), together with a known norsesquiterpene (5) were isolated from the rhizomes of Curcuma phaeocaulis. Their structures were established based on extensive spectroscopic analysis. Compounds 1 and 5, as far as we know, are the first example of 13-norguaiane-type sesquiterpenes isolated from the genus Curcuma. All of the isolated compounds were tested for inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages. Compound 1 showed strong inhibitory activity on nitric oxide production with IC₅₀ value of 3.58 ± 0.17 μM.     

New biphenyl derivatives from the leaves of Nicotiana tabacum and their cytotoxic activity

With the aim of searching for new bioactive metabolites from medicinal plants, three new biphenyls, tababiphenyls G–I (1–3), together with four known ones (4–7) were isolated from the leaves of Nicotiana tabacum. Their structures were elucidated by extensive NMR and MS spectroscopic analyses. All the isolated compounds were evaluated for their cytotoxicity against NB4, A549, SHSY5Y, PC3, and MCF7 human cancer cell lines, and some of them showed moderate inhibitory activities against several human tumor cell lines with IC₅₀ values ranging from 2.8 to 9.4 μM.     

Triterpenoids in Gypsophila trichotoma Wend.

A new triterpeniod saponin 3-O-β-arabinopyranosyl-(1 → 3)-[β-galactopyranosyl-(1 → 2)]-β-glucuronopyranosyl gypsogenin (1), together with the known saponin 3-O-β-xylopyranosyl-(1 → 3)-[β-galactopyranosyl-(1 → 2)]-β-glucuronopyranosyl gypsogenin (2), and three known triterpenes gypsogenic acid (3), quillaic acid (4) and gypsogenin (5) were isolated from the roots of Gypsophila trichotoma Wend. (Caryophyllaceae). Their structures were elucidated by chemical and spectral methods. Cytotoxic activity of compounds 1 and 2 were tested against seven human cancer cell lines. Compound 1 showed cytotoxic activity against all of them, while compound 2 only against two cell lines.     

In vitro growth inhibitory effects of 13,28-epoxyoleanane triterpene saponins in cancer cells

Two new 13,28-epoxyoleanane triterpene saponins, magnosides A (1) and B (2), were isolated from the 95% ethanolic extract of Cybianthus magnus (Mez) Pipoly roots. Their structures were deduced by a combination of spectral analyses and chemical evidences as compared to data reported in the literature. The hemolytic activity of both compounds was measured. Compound 1 was shown to exhibit the strongest hemolytic activity with a HD₅₀ of 3.8 μM followed by 2 with a HD₅₀ of 33.5 μM. The bioactivity of compounds 1 and 2 was also evaluated in vitro against different cellular models including Mycobacterium tuberculosis, Leishmania amazonensis axenic amastigotes, mouse peritoneal macrophages and eight cancer cell lines. While neither of the tested compounds displayed any activity against M. tuberculosis, both exhibited anti-leishmanial activity against axenic amastigotes as well as in vitro growth inhibitory activity against all tested cancer cell lines with IC₅₀ growth inhibitory concentrations ranging between 4 μM and 33 μM. The compounds displayed similar growth inhibitory activity in cancer cell lines sensitive to pro-apoptotic stimuli versus those displaying various levels of resistance to such stimuli. Quantitative videomicroscopy analyses revealed that compounds 1 and 2 are cytotoxic.     

A new lignan and a new alkaloid,and α-glucosidase inhibitory compounds from the grains of Echinochloa utilis Ohwi & Yabuno

A new lignan, utilisin (1), and a new alkaloid, echinoutilin (2), together with eleven known compounds 3–13 were isolated from the grains of Echinochloa utilis Ohwi & Yabuno. Their structures were identified through the analysis of spectroscopic data. The absolute configuration of 2 was determined by Mosher’s method. These compounds were evaluated for α-glucosidase inhibitory activity. Among them, compounds 2, 3 and 6 exhibited considerable α-glucosidase inhibitory activity with IC₅₀ values of 42.1 ± 1.3, 58.9 ± 3.7, and 40.9 ± 1.1 μM, respectively. The results indicate that the grains of E. utilis will be useful in the treatment of diabetes control agents.