Cytotoxic cytochalasans from Aspergillus flavipes PJ03-11 by OSMAC method

Two new cytochalasans flavichalasine N (1), flavichalasine O (2), together with six known cytochalasans (3–8), were isolated from Aspergillus flavipes PJ03-11 through the application of OSMAC (one strain many compounds) strategy. Flavichalasine O (2) represented the first example of cytochalasans possessing a nitrogen-oxygen heterocycle at the macrocyclic ring part. Their structures were established on the base of extensive spectroscopic analysis. Compounds 1–4 exhibited significant cytotoxic activities against three human cancer cell lines (THP1, HL-60 and PC3) with IC₅₀ values ranging from 3.00 to 15.10?μM.     

Cytotoxic and anti-inflammatory diterpenoids from the Dongsha Atoll soft coral Sinularia flexibilis

Seven new diterpenoids, namely, flexibilisolides C–G (1–5), flexibilisin C (6), and a novel 11,12-secoflexibillin (7), along with seven known compounds, 8–14, were isolated from the Dongsha Atoll soft coral Sinularia flexibilis. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and comparison of the NMR data with those of known analogues. Compounds 1, 8, and 11 were shown to exhibit moderate cytotoxic activity against HeLa and B16 cancer cell lines, and compound 10 was found to exhibit more potent cytotoxic activity against SK-Hep1 and B16 cancer cell lines. Moreover, compounds 1, 2, 8, 9, and 11–14 could significantly inhibit the accumulation of the pro-inflammatory iNOS protein and 1, 8, 11, and 14 could reduce the accumulation of COX-2 protein in LPS-stimulated RAW264.7 macrophage cells.     

Rakicidins G - I,cyclic depsipeptides from marine Micromonospora chalcea FIM 02-523

Rakicidins G-I (1–3), three new cyclic depsipeptides including a long aliphatic chain without terminal methyl branching were isolated from culture broth of Micromonospora chalcea FIM 02–523, along with rakicidin E (4). Their structures were elucidated by extensive NMR and HR-ESI-MS analyses. Compounds 1–4 were evaluated for their cytotoxic activities against HCT-8 and PANC-1 human tumor cell lines under the hypoxic and normoxic conditions. They were approximately 18.2–20.3-fold more cytotoxic under hypoxic than under normoxic conditions on PANC-1, and compared with 7.4–8.7-fold more cytotoxic under hypoxic than under normoxic conditions on HCT-8. Meanwhile, compounds 1–3 were also tested inhibitory activities against gram positive anaerobic bacteria and the results exhibited MIC values in the range of 0.125–8?μg/mL.     

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.     

In vitro anthelmintic and cytotoxic activities of extracts from the stem barks of Berlinia confusa (C. Hoyle) and identification of its active constituents

Phytochemical investigation of EtOAc extract from the stem bark of Berlinia confusa yielded a new and two known polysaturated monoacylglycerides characterised as 1-O-docosanoyl-sn-glyceride (3), 1-O-(13-methyltetradecanoyl)-sn-glycerol (4) and 1-O-pentadecacanoyl-sn-glycerol (5); along with the known compounds betulinic acid (1) and sitosteryl-β-d-glucoside (2). The structures of these compounds were elucidated using analytical methods, including 1D and 2D-NMR together with MS spectroscopy. The extracts and isolated compounds demonstrated concentration-dependent anthelmintic activities against Fusciola gigantica (liver flukes) and Taenia solium (tapeworm) at 10–100 mg/ml. The extracts and isolated compounds were evaluated for cytotoxicity against a small panel of three human tumour cell lines.     

Pellynols M−O,cytotoxic polyacetylenic alcohols from a Niphates sp. marine sponge

Three new polyacetylenic alcohols, pellynols M?O (1–3), along with two known ones, melyne A (4) and melyne B (5), were isolated from a Niphates sp. marine sponge collected off the South China Sea. The structures of new compounds were determined based on a combination of 1D and 2D NMR analysis, ESI-MSⁿ fragmentation, and chemical (ozonolysis) method. Their absolute configurations were assigned by modified Mosher's method. All the isolates showed potent cytotoxic activity against PC9 and HepG2 human cancer cell lines with IC₅₀ values of 2.9–7.6?μM.     

Kadpolysperins A–N,lanostane triterpene acids possessing rich structure types from Kadsura polysperma

Fourteen new lanostane triterpene acids (1–14), and five known analogues (15–19) were isolated from the stems of Kadsura polysperma. Compound 1, with a rearranged tetracyclic skeleton, is an important biogenic precursor of longipedlactone skeleton. Compounds 2–6 are members of 18(13→12)-abeo-lanostane triterpene acids. The structures of new compounds were elucidated by spectroscopic evidence. Selected compounds were evaluated for their in vitro cytotoxicity against human tumor HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cell lines.     

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.     

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.     

Cytotoxic labdane diterpenes and bisflavonoid atropisomers from leaves of Araucaria bidwillii

Chemical investigation of a methanolic extract of leaves from Araucaria bidwillii (Araucariaceae) from Egypt afforded four new labdane diterpenoidal metabolites (1–4) together with one known diterpene, 7-oxocallitrisic acid (5), two triterpenoidal metabolites, 2-O-acetyl-11-keto-boswellic acid (6) and β-sitosterol-3-O-glucopyranoside (7), phloretic acid (8), and two methylated bisflavonoids, agathisflavone-4′,7,7″-trimethyl ether (9) and cupressuflavone-4′,7,7″-trimethyl ether (10). The new metabolites 1–4 were unambiguously identified by applying extensive 1D and 2D NMR spectroscopic studies as well as HRESIMS. The relative and absolute configurations of 1–4 were determined using ROESY and the modified Mosher's method, respectively. All isolated compounds were assessed for their antimicrobial, antitubercular and cytotoxic activities. Among the tested compounds, the new labdane diterpenes 1–4 revealed significant cytotoxic activity against mouse lymphoma L5178Y cell line with IC₅₀ values ranging from 1.4 to 12.9 μM, respectively.     

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.     

Talarophenol sulfate and talarophilones from the Australian mud dauber wasp-associated fungus,Talaromyces sp. CMB-W045

Chemical analysis of a jasmine rice cultivation of an Australian mud dauber wasp-associated fungus, Talaromyces sp. CMB-W045, led to the discovery of a new p-terphenyl, talarophenol sulfate (1). The structure elucidation of 1 was achieved by detailed spectroscopic analysis supported by acid hydrolysis to the p-hydroquinone talarophenol (2), and subsequent in situ air oxidation to trace amounts of the p-quinone talaroquinone (3). The same jasmine rice cultivation also yielded the new talarophilones A (4) and B (5), and known (+)-mitorubrin (6) and pochonin D (7), with structures assigned by detailed spectroscopic analysis. Neither 1 or 4–7 exhibited growth inhibitory properties against a panel of human cell lines, or bacterial or fungal pathogens, although 1 did exhibit selective antibacterial activity against Streptococcus pyogenes ATCC 12344 (IC₅₀ 10 µM).     

<em>Mesua beccariana </em>(Clusiaceae), A Source of Potential Anti-cancer Lead Compounds in Drug Discovery

An investigation on biologically active secondary metabolites from the stem bark of Mesua beccariana was carried out. A new cyclodione, mesuadione (1), along with several known constituents which are beccamarin (2), 2,5-dihydroxy-1,3,4-trimethoxy anthraquinone (3), 4-methoxy-1,3,5-trihydroxyanthraquinone (4), betulinic acid (5) and stigmasterol (6) were obtained from this ongoing research. Structures of these compounds were elucidated by extensive spectroscopic methods, including 1D and 2D-NMR, GC-MS, IR and UV techniques. Preliminary tests of the in vitro cytotoxic activities of all the isolated metabolites against a panel of human cancer cell lines Raji (lymphoma), SNU-1 (gastric carcinoma), K562 (erythroleukemia cells), LS-174T (colorectal adenocarcinoma), HeLa (cervical cells), SK-MEL-28 (malignant melanoma cells), NCI-H23 (lung adenocarcinoma), IMR-32 (neuroblastoma) and Hep-G2 (hepatocellular liver carcinoma) were carried out using an MTT assay. Mesuadione (1), beccamarin (2), betulinic acid (5) and stigmasterol (6) displayed strong inhibition of Raji cell proliferation, while the proliferation rate of SK-MEL-28 and HeLa were strongly inhibited by stigmasterol (6) and beccamarin (2), indicating these secondary metabolites could be anti-cancer lead compounds in drug discovery.     

Spiroketals,isocoumarin, and indoleformic acid derivatives from saline soil derived fungus Penicillium raistrickii

Six new compounds, named peneciraistins A–F (1–6), were isolated from saline soil derived fungus Penicillium raistrickii. Among them, compounds 1 and 2 are rare benzannulate 6,6-spitoketals, and compounds 5 and 6 are the first naturally occurring 3-indoleformic acid derivatives. Their structures were elucidated by means of their detailed NMR and MS spectroscopic data. Their absolute configurations were assigned by the modified Mosher method, CD excitation chirality method or optical rotation by comparison with those of known compounds. Their cytotoxicities were also reported against A549 and MCF-7 cell lines along with radical scavenging activities against DPPH (1,1-diphenyl-2-picrylhydrazyl).     

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.     

seco-Polycyclic polyprenylated acylphloroglucinols with unusual carbon skeletons from Hypericum ascyron

Three new seco-polycyclic polyprenylated acylphloroglucinols (PPAPs), ascyronones A–C (1–3), and a new biosynthetic precursor, ascyronone D (4), were isolated from Hypericum ascyron together with three known analogues (5–7). Compounds 1 and 2, sharing an unusual seven-membered carbon core fused with a γ-lactone ring, could be derived from 1,9-seco-PPAPs via further rearrangement. A biomimetic transformation from 5 to 1 was performed by using base-driven retro-Claisen and rearrangement cascade reaction, which further confirmed the structure of 1 and shed light to its possible biosynthetic pathway. Interestingly, all these compounds are decorated with a methyl group at C-5 instead of a prenyl or geranyl group in many other PPAPs. The isolates were evaluated for their inhibitory activities against five human tumor cell lines.     

Nortriterpene constituents from Schisandra sphenanthera

Nine new highly oxygenated nortriterpenoids, pre-schisanartanins E–J (1–6) and sphenadilactones D–F (7–9), together with 17 known ones (10–26), have been isolated from the acetone extract of the roots and stems of Schisandra sphenanthera. The structures of the new metabolites were characterized on the basis of extensive spectroscopic analyses including 1D and 2D NMR experiments. These compounds were all evaluated for their cytotoxicity against HL-60, SMMC-7721, A549, MCF-7, and SW480 tumor cell lines.     

Structurally diverse diterpenoids from Isodon ternifolius collected from three regions

Phytochemical investigation of the aerial parts of Isodon ternifolius from three regions in Yunnan Province afforded 9 new diterpenoids, ternifoliusins A–I (1–9), together with 26 known diterpenoids. Among them, ternifoliusins A–D possess rare 6,7:8,15-diseco-7,20-olide-6,8-cyclo-ent-kaurane diterpenoid scaffold. The structures of all compounds were determined by comprehensive spectroscopic analysis, as well as quantum chemical calculation methods. Moreover, the molecular constitutions and configurations of ternifoliusins A, E, and F (1, 5, 6) were confirmed by single-crystal X-ray diffraction analysis. Ten compounds were assayed for their cytotoxic activity against the HL-60, SMMC-7721, A-549, MCF-7, and SW-480 human tumor cell lines, and compounds 13, 17, 19, 20, 31 and 34 were demonstrated to be active against all of the five human tumor cell lines.     

Polyketide anthraquinone,diphenyl ether,and xanthone derivatives from the soil fungus Penicillium sp. PSU-RSPG99

Three new polyketides including one new diphenyl ether, penicillither (1), one new anthraquinone, penicilliquinone (2), and one new xanthone, penicillixanthone (3), together with twelve known compounds were isolated from the soil fungus Penicillium sp. PSU-RSPG99. Their structures were identified by spectroscopic evidence. In addition, the position of a chlorine atom in 1 was confirmed by the plausible biosynthetic pathway from the isolated chlorobenzophenone. Known GKK1032B displayed mild antimycobacterial and moderate cytotoxic (against human oral carcinoma, KB, human breast cancer, MCF-7, and noncancerous Vero cell lines) activities.     

Sesquiterpenoid with new skeleton from Chloranthus henryi

Dayejijiol (1), a novel sesquiterpene with a new carbon skeleton, and a novel labdane-type diterpenoid (13S)-13-hydroxy-19-methoxy-5αH-8(17), 14-labdadien (3), together with three known compounds chloranthalactone A (4), shizukanolide (5), shizukolidol (6) were isolated from Chloranthus henryi Hemsl. Their structures were established by a combination of 1D and 2D NMR spectroscopic techniques. Compounds 1 and 5 exhibited anti-tumor activities against Hela and K562 human tumor cell lines.