Cytotoxic sesquiterpenes from luminescent mushroom Neonothopanus nambi

Four new aristolane sesquiterpenes named nambinones A–C (1–3) and 1-epi-nambinone B (4), a new sesquiterpene, nambinone D (5), a known compound, aurisin A (6) as well as a new dimeric sesquiterpene, aurisin K (7), were isolated from two isolates of luminescent mushroom, Neonothopanus nambi, PW1 and PW2. These structures were established on the basis of spectroscopic evidence. The relative configuration of 6 was determined by X-ray crystallographic analysis. Compounds 6 and 7 exhibited antimalarial activity against Plasmodium falciparum and antimycobacterial activity against Mycobacterium tuberculosis. Compounds 3, 6, and 7 showed cytotoxicity against NCI-H187 cancer cell lines. In addition, 6 and 7 showed cytotoxicity against the cholangiocarcinoma cell lines.     

Cytotoxic arylbenzofuran and stilbene derivatives from the twigs of Artocarpus heterophyllus

Four new natural products, including three arylbenzofurans named heterophyllenes A-C (1–3), and one stilbene named heterophyllene D (4), together with twenty-one known compounds were isolated from the twigs of Artocarpus heterophyllus and their structures elucidated by spectroscopic methods, mainly 1D and 2D NMR spectroscopy. The cytotoxic activity of selected compounds against KB, MCF-7 and NCI-H187 cell lines was evaluated. Heterophyllene C (3) exhibited cytotoxicity against the MCF-7 cell line with an IC₅₀ value of 12.56 μM. Additionally, the known compounds norartocarpin and artocarpin showed cytotoxic activity against MCF-7 and KB cell lines with IC₅₀ values of 10.04 and 13.57 μM, respectively. Both compounds also displayed cytotoxicity against the NCI-H187 cell line with values of 14.78 and 14.21 μM, respectively.     

Meloslines A and B,two novel indole alkaloids from Alstonia scholaris

An unprecedented indole alkaloid melosline A (1), with 6/5/6/6 tetracyclic ring skeleton, together with a new alkaloid melosline B (2) and one known compound (3) were isolated from the leaves and twigs of Alstonia scholaris. The new structures were elucidated by comprehensive spectroscopic analysis. The absolute configuration of compound 1 was confirmed by comparison of experimental data with calculated electronic circular dichroism (ECD). Compound 1 exhibited moderate cytotoxicity against MCF-7 cancer cell lines.     

New polycyclic tetramate macrolactams from marine-derived Streptomyces sp. SCSIO 40060

Polycyclic tetramate macrolactams (PTMs) are widely distributed in nature and are generated from a compact biosynthetic pathway. Bioinformatics analysis of the draft genome sequence of marine-derived Streptomyces sp. SCSIO 40060 revealed the presence of a putative PTM-encoding biosynthetic gene cluster (BGC). Comparison of this PTM BGC with those from the databank by genome mining suggests that Streptomyces sp. SCSIO 40060 should produce PTMs with a 5/6/5 type of carbocyclic ring. Subsequently, a 40-L scale of cultivation of Streptomyces sp. SCSIO 40060 led to the isolation and characterization of four known PTMS, ikarugamycin (1), epoxyikarugamycin (2), capsimycin (3), capsimycin C (4), and three new PTMs, hydroxyikarugamycins A–C (5–7). The planar structures of 5–7 were assigned by comprehensive spectroscopic analysis and the absolute configurations of 5 and 6 were unequivocally determined by X-ray diffraction analysis. The absolute structure of 7 was deduced by comparing ECD spectra of 5–7. Capsimycin (3) showed antimicrobial activity against methicillin-resistant Staphylococcus aureus with a MIC value of 16?μg/mL and displayed cytotoxicity against several cancer cell lines with IC₅₀ values ranging from 2.62 to 6.87?μM.     

Erysacleuxins C and D,new isoflavones from the twigs of Erythrina sacleuxii Hua and their cytotoxic activity

Two previously undescribed isoflavones, erysacleuxin C (1) and erysacleuxin D (2), together with seven known compounds (3–9), were isolated and identified from the EtOAc extract of the twigs of Erythrina sacleuxii Hua (Leguminosae). The structures of the isolated compounds were determined on the basis of their spectroscopic and spectrometric data. Evaluation of their cytotoxicity against the human cancer HeLa-S3 cell lines indicated IC₅₀ values of 130.4, 54.9 and 73.9 µM for erysacleuxin C (1), erysacleuxin D (2) and butin (9), respectively.     

Physalinol A,a 1,10-seco-physalin with an epidioxy from Physalis alkekengi L. var. franchetii (Mast.) Makino

Physalinol A (1), a novel 1, 10-seco-physalin with a peroxy bridge, was isolated from the organic extracts of Physalis alkekengi L. var. franchetii (Mast.) Makino. The structure was determined on the basis of 1D and 2D NMR spectra and HR-ESI-MS data. The absolute configuration of 1 was evidenced by X-ray diffraction data and further confirmed by ECD calculations. The isolated compound 1 has no cytotoxicity against HCT-116 and PC-3 cancer cell lines and a weak antimicrobial activity against Escherichia coil. In addition, compound 1 also exhibited a weak anti-inflammatory action in lipopolysacaride (LPS)-induced RAW 264.7 macrophages with an IC₅₀ value of 57.3?±?1.03?μM.     

Cytotoxic Podophyllotoxin Type-Lignans from the Steam Bark of <em>Bursera fagaroides </em>var. <em>fagaroides</em>

The hydroalcoholic extract of the steam bark of B. fagaroides var. fagaroides displayed potent cytotoxic activity against four cancer cell lines, namely KB (ED₅₀ = 9.6 × 10^-2 μg/mL), PC-3 (ED₅₀ = 2.5 × 10^-1 μg/mL), MCF-7 (ED₅₀ = 6.6 μg/mL), and HF-6 (ED₅₀ = 7.1 × 10^-3 μg/mL). This extract also showed anti-tumour activity when assayed on mice inoculated with L5178Y lymphoma cells. Bioactivity-directed isolation of this extract, afforded seven podophyllotoxin-type lignans identified as podophyllotoxin (1), β-peltatin-A-methylether (2), 5'-desmethoxy-β-peltatin-A-methylether (3), desmethoxy-yatein (4), desoxypodophyllotoxin (5), burseranin (6), and acetyl podophyllotoxin (7) by 1D and 2DNMR and FAB-MS analyses, and comparison with reported values. All the isolated compounds showed potent cytotoxic activity in the cell lines tested, especially compound 3, which exhibited greater activity than camptothecin and podophyllotoxin against PC-3 (ED₅₀ = 1.0 × 10^-5 μg/mL), and KB (ED₅₀ = 1.0 × 10^-5 μg/mL). This is the first report of the isolation of podophyllotoxin and its acetate in a Bursera species.     

Nitricquinomycins A-C,uncommon naphthopyrrolediones from the Streptomyces sp. ZS-A45

Nitricquinomycins A-C (1～3), three uncommon naphthopyrrolediones, together with one new compound (4), were isolated from the modified rice solid fermentation of the marine-derived Streptomyces sp. ZS-A45, an actinobacterium isolated from the marine sediments collected from Zhoushan island. Their structures were elucidated on the basis of MS, NMR spectroscopic and quantum chemical calculations of the electronic circular dichroism (ECD) spectra. Compounds 3 and 4 exhibited significant cytotoxicity against A2780 cell lines with IC₅₀ values of 4.77 and 2.92 μM, respectively; on the other hand, compound 3 exhibited moderate antibacterial activities against Escherichia coli, Staphylococcus aureus and Candida albicans with MIC values of 20.0 40.0 and 40.0 μM, respectively.     

Polyhydroxylated steroids from the octocoral Isis hippuris

The specimens for previous studies on the secondary metabolites of the Formosan octocoral Isis hippuris were all collected at Green Island. In the course of our studies on bioactive compounds from marine organisms, the acetone-solubles of the Formosan octocoral I. hippuris collected at Orchid Island has led to the isolation of six new polyoxygenated steroids (1-6), along with a known compound 7. Compound 6 possesses a new type of steroid side chain moiety. The structures of these compounds were determined on the basis of their spectroscopic and physical data. The anti-HCMV (human cytomegalovirus) activity and cytotoxicity against selected cell lines of 1-7 were evaluated. Compound 3 exhibited inhibitory activity against HCMV, with an EC₅₀ values of 2.0 μg/mL, respectively. Compound 7 displayed cytotoxicity against P-388 and A-549 cell lines with ED₅₀ values of 3.2 and 3.86 μg/mL, respectively.     

Alokicenones A-H,eight tetrahydroanthracenes from the mangrove-derived Streptomyces sp. HN-A101

Alokicenones A-H (1–8), eight new tetrahydroanthracenes and one known okicenone (9) were identified from the secondary metabolites of mangrove-derived Streptomyces sp. HN-A101. Their structures were elucidated by HRESIMS and NMR spectroscopic data. The absolute configurations of them were determined by the calculated and experimental ECD curves. Compounds 1–2 and 9 showed moderate cytotoxicity against HCT116 and SW620 cancer cell lines with IC₅₀ values from 0.63 to 7.73?μM. In addition, compounds 1–3 and 7–9 also exhibited inhibitory activities against ROCK2 or BRD4.     

Halichoblelides B and C,potent cytotoxic macrolides from a Streptomyces species separated from a marine fish

Halichoblelide B (1) and C (2), novel macrolides with potent cytotoxicity against tumor cells in culture, have been isolated from a strain of Streptomyces hygroscopicus originally derived from the marine fish Halichoeres bleekeri, and their absolute stereostructures have been elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and chemical transformations. These compounds exhibited significant cytotoxicity against human cancer cell lines.     

Ecionines A and B, two new cytotoxic pyridoacridine alkaloids from the Australian marine sponge, Ecionemia geodides

Chemical investigations of the Australian marine sponge Ecionemia geodides resulted in the isolation of two new pyridoacridine alkaloids, ecionines A (1) and B (2), along with the previously isolated marine natural products, biemnadin (3) and meridine (4). Compounds 1 and 2 both contain an imine moiety, which is rare for the pyridoacridine structure class. The chemical structures of 1 and 2 were determined by extensive 1D and 2D NMR and MS data analyses. All compounds were tested against a panel of human bladder cancer cell lines, the increasingly metastatic TSU-Pr1 series (TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1-B2) and the superficial bladder cancer cell line 5637. Ecionine A (1) displayed cytotoxicity against all cell lines, with IC₅₀ values ranging from 3 to 7 μM. This is the first report of chemistry from the sponge genus Ecionemia.     

Two lignans,one alkaloid,and flavanone from the twigs of Feroniella lucida

Four new compounds, two lignans; lucidenal and lucidanin (1 and 2), one alkaloid (3), and one flavanone (4) together with 26 known compounds (5–30), were isolated from the twigs of Feroniella lucida. The structures of the new compounds were determined on the basis of spectroscopic analyses. Lucidenal 1 showed cytotoxicity against HuCCA-1, A549, MOLT-3 and HepG2 cancer cell lines with IC₅₀ values of 4.27, 9.59, 2.31, and 6.50 μg/mL, respectively. A plausible biosynthetic pathway of 1 was proposed.     

Cespitulactams A, B, and C, three new nitrogen-containing diterpenes from Cespitularia taeniata May

Three new nitrogen-containing diterpenoids, designated cespitulactams A (1), B (2), and C (3), were isolated from Cespitularia taeniata May. Compounds 1-3 are novel structures having a phenylethyl amino side at C-10 and with an amide function at C-20. Their structures were determined on the basis of extensive spectroscopic analysis and chemical correlation. The cytotoxicity of 1 and its monoacetate (6) were also evaluated against human cancer cell lines.     

Two new sesquiterpenes and six norsesquiterpenes from the solid culture of the edible mushroom Flammulina velutipes

One new sesquiterpene with a novel carbon skeleton, flammulinol A (1), one new isolactarane sesquiterpene and six isolactarane-related norsesquiterpenes, flammulinolides A–G (2–8), as well as sterpuric acid, were isolated from the solid culture of Flammulina velutipes. The structures of the new compounds were elucidated by spectroscopic methods. The absolute configuration of C-3 in 1 was determined via the circular dichroism data analysis based on the octane rule of cyclopentenone, whereas the absolute configurations of compounds 2, and 5–8 were assigned using the circular dichroism data of the [Rh₂(OCOCF₃)₄] complex. Compounds 2, 3, and 7 showed strong cytotoxicity against KB cell line with the IC₅₀ of 3.9, 3.6, and 4.7 μM, respectively. Compound 4 showed strong cytotoxicity against Hela cell line with the IC₅₀ of 3.0 μM. The plausible biosynthetic pathway for 2–9 in F. velutipes was discussed.     

Cyclopeptides and polyketides from coral-associated fungus, Aspergillus versicolor LCJ-5-4

Three new cyclopentapeptides, versicoloritides A-C (1-3), a new orcinol tetramer, tetraorcinol A (4), and two new lactones, versicolactones A and B (5 and 6) together with three known metabolites, diorcinol, glyantrypine, and cordyol C were isolated from the fermentation broth of the coral-associated fungus Aspergillus versicolor LCJ-5-4. Their structures were elucidated by spectroscopic and chemical methods. The new compounds 1-4 were evaluated for their radical-scavenging activity and antimicrobial activity against Staphylococcus aureus, Escherichia coli, Enterobacter aerogenes, Bacillus subtilis, Pseudomonas aeruginosa, and Candida albicans and cytotoxicity against P388 and Hela cell lines. Compound 4 showed weak radical-scavenging activity against the DPPH radical with an IC₅₀ value of 67 μM.     

Chemical-epigenetic method to enhance the chemodiversity of the marine algicolous fungus, Aspergillus terreus OUCMDZ-2739

Four new meroterpenoids identified as (R)-4-((2,2-dimethylchroman-6-yl)methyl)-3-(4-hydroxyphenyl)-5-methoxyfuran-2(5H)-one (1), 1-(2,2-dimethylchroman-6-yl)-3-(4-hydroxyphenyl)propan-2-one (2), (R,E)-3-(2,2-dimethylchroman-6-yl)-4-hydroxy-5-((2-(2-hydroxypropan-2-yl)-2,3-dihydrobenzofuran-5-yl)methylene)furan-2(5H)-one (3), methyl (R)-2-(2-(2-hydroxypropan-2-yl)-2,3-dihydrobenzofuran-5-yl) acetate (4), along with nine known compounds (5–13) were isolated from a chemical-epigenetic culture of Aspergillus terreus OUCMDZ-2739 with 10 μM trichostatin A (TSA). Under the same condition without TSA, A. terreus OUCMDZ-2739 produced different compounds (14–20), supporting that the chemical-epigenetic modification of fungi could enrich the chemodiversity of the fungal products. The cytotoxicity was observed for compound 8 against K562 cell, 9 against MCF-7 and K562 cells and 12 against MCF-7 cell with IC₅₀ values of 9.5, 10.1, 13.0 and 8.5 μM, respectively. Compounds 3, 8 and 17 exhibited stronger α-glucosidase inhibition than 1-deoxynojirimycin and acarbose (positive controls) with IC₅₀ values of 24.8, 1.2, 61.6, 191.7 and 555.1 μM, respectively. The enzyme kinetics study further indicated that compound 8 was an anticompetitive inhibitor with K_i value of 1.42 μM.     

A rearranged seco-steroid with new skeleton and five new abnormal progesteroids from Nodulisporium sp.

Abeo-nodulisporisteroid A (1), an abnormal steroid with a rearranged C3 chain at C-9 possibly derived from seco-ring A via Wagner-Meerwein rearrangement and oxidations, was obtained from Nodulisporium sp. together with five related new seco-progesteroids (nodulisporisteroids M-Q, 2–6), which were elucidated by the extensive spectroscopic analysis and X-ray crystallography. A plausible biosynthetic pathway of 1–6 was also proposed. Furthermore, these isolated compounds were also evaluated for cytotoxicities against five human tumour cell lines, antimicrobial activities, and inhibitions against PI3K gamma, Aβ₄₂ aggregation, and α-glucosidase.     

Three new inositol derivatives from Chisocheton paniculatus

Three new inositol derivatives (1–3) were isolated from the leaves of Chisocheton paniculatus collected in Vietnam, along with four known compounds, including a limonoid (4), two triterpenoids (5–6), and a tocopherol (7). The structures of the new compounds were elucidated by 1D- and 2D-NMR and HRESIMS analyses. Compound 4 showed the highest cytotoxicities against the human lung cancer A549 and cervical cancer HeLa cell lines, with IC₅₀ values of 7.3 and 8.8 µM, respectively, among the isolated compounds. Compounds 5 and 7 displayed moderate to weak cytotoxicities against the A549, HeLa, and human stomach cancer GSU cell lines, with IC₅₀ values ranging from 17.7 to 68.0 µM.     

Premnalatifolin A, a novel dimeric diterpene from Premna latifolia Roxb

Premnalatifolin A (1), a unique icetexane diterpene dimer was isolated from the stem-bark of Indian medicinal plant, Premna latifolia. Its structure and relative stereochemistry were elucidated on the basis of detailed spectroscopic analysis, including HRESIMS and 2D NMR (COSY, HSQC, HMBC, and NOESY) spectra. The compound has dimeric carbon skeleton composed of two icetexane skeletal diterpenes linked via ether bond. Further, premnalatifolin A (1) was also evaluated for its cytotoxicity against cancer cell lines (HT-29, A-431, MCF-7, Hep-G2, PC-3, A-549, B-16 F10, and ACHN), which displayed potent activity against HT-29 and MCF-7 cell lines with the IC₅₀ values of 12.15 and 1.11 μg/mL, respectively.