Trichothecenes from the fungus Acremonium crotocinigenum BCC 20012

Two new trichothecenes (1 and 2) and a new chloroderivative of a trichothecene analogue (3) together with four known trichothecenes, crotocin, trichothecin, 8-deoxytrichothecinol B, and a trichothecene analogue, were isolated from the fungus Acremonium crotocinigenum BCC 20012. The structures of these compounds were elucidated by extensive spectroscopic analysis. Among the tested metabolites, trichothecin itself showed strongest antimalarial activity against Plasmodium falciparum K1, and cytotoxic activity against Vero cell lines with IC₅₀ values of 0.05 and 0.13 μg/mL, respectively.     

Myrotheciumones: Bicyclic cytotoxic lactones isolated from an endophytic fungus of Ajuga decumbens

Two new bicyclic lactones, myrotheciumones A (1) and B (2) which possessed a rare ring-fusion system were isolated from Myrothecium roridum (M. roridum), an endophytic fungus of the medicinal herb plant Ajuga decumbens (A. decumbens) via an in vitro cytotoxicity assay. Structures were deduced from 1D and 2D NMR (Nuclear magnetic resonance) data. Myrotheciumone A’s in vitro cytotoxicity and apoptotic activity were evaluated and myrotheciumone A was shown to exert cytotoxicity via inducing apoptosis in cancer cell line.     

Acetalation of d-glucitol: 2,3:5,6-Di-O-isopropylidene-d-glucitol

The reaction of d-glucitol with acetone-zinc chloride gave a mixture of isopropylidene derivatives, from which the 2,3:5,6-diacetal (12) could be separated as its 1,4-dimesylate (13) or 1,4-ditosylate (14). The structure of 12 was proved by converting 14, via the 1-mono-iodide, into the known 1-deoxy-d-glucitol, and by mass-spectrometric investigation of the 1-deoxy-4-O-methyl diacetal. The terminally situated acetal group in 12 can be selectively hydrolyzed, and, on treatment with base, the 5,6-dihydroxy derivative obtained gives a d-galactitol 4,5-epoxide derivative.     

Cyclic heptapeptides from the soil-derived fungus Clonostachys rosea

Three new cyclic heptapeptides (1–3) together with three known compounds (4–6) were isolated from a solid rice culture of the soil-derived fungus Clonostachys rosea. Fermentation of the fungus on white beans instead of rice afforded a new γ-lactam (7) and a known γ-lactone (8) that were not detected in the former extracts. The structures of the new compounds were elucidated on the basis of 1D and 2D NMR spectra as well as by HRESIMS data. Compounds 1 and 4 exhibited significant cytotoxicity against the L5178Y mouse lymphoma cell line with IC₅₀ values of 4.1 and 0.1 µM, respectively. Compound 4 also displayed cytotoxicity against the A2780 human ovarian cancer cell line with an IC₅₀ value of 3.5 µM. The preliminary structure-activity relationships are discussed.     

One pot three components microwave assisted and conventional synthesis of new 3-(4-chloro-2-hydroxyphenyl)-2-(substituted) thiazolidin-4-one as antimicrobial agents

A one-pot, three-component, microwave assisted and conventional synthesis of new 3-(4-chloro-2-hydroxyphenyl)-2-(substituted) thiazolidin-4-one (4a–n) was carried out by using N,N-dimethylformamide as a solvent with high product yield. Among these synthesized compounds (4f, 4g, 4l and 4m) were found to be a broad spectrum molecule active against all bacterial and fungus strains tested, except fungus Aspergillus niger. Amongst the compounds (4g, 4l and 4m) were found to be more potent than respective standard drugs used in the experiment against Candida albicans, Staphylococcus aureus and Aspergillus flavus, respectively. All synthesized compounds were also tested for their cytotoxic activity against HeLa and MCF-7 cell lines by the sulforhodamine B (SRB) assay. This study shows that all compounds were non-cytotoxic in nature, and confirmed their antimicrobial specificity apart from any general cytotoxicity.     

Identification of spirobisnaphthalene derivatives with anti-tumor activities from the endophytic fungus Rhytidhysteron rufulum AS21B

The cultivation of the mangrove-derived fungus Rhytidhysteron rufulum AS21B in acidic condition changed its secondary metabolite profile. Investigation of the culture broth extract led to the isolation and identification of two new spirobisnaphthalenes (1 and 2) together with eleven known compounds (3–13) from the crude extract of the fungus grown under an acidic condition as well as six known compounds (4, 10, 14–17) were isolated from the crude extract of the fungus grown under a neutral condition. Their structures were elucidated on the basis of extensive spectroscopic data. The isolated compounds were evaluated for their cytotoxicity against two human cancer cell lines, Ramos lymphoma and drug resistant NSCLC H1975. Compounds 2 and 10 displayed the most promising anti-tumor activity against both cancer cell lines.     

Biotransformation of 20(R)-panaxatriol by Aspergillus niger AS 3.739

Microbial transformation of 20(R)-panaxatriol (PT) was performed by using the fungus Aspergillus niger AS 3.739. Six metabolites (1–6) including five new compounds were obtained. The chemical structures of these transformed products were elucidated based on various spectroscopic analyses, including 1D and 2D NMR and HRESI-MS. Metabolites 2–6 are new compounds. Furthermore, metabolites 2, 3, 5, and 6 exhibited significant anti-hepatic fibrosis activity, while 4 showed cytotoxicity against HSC-T6 cells.     

Anthraquinone derivatives from the mangrove-derived fungus Phomopsis sp. PSU-MA214

One new tetrahydroanthraquinone derivative, (2R,3S)-7-ethyl-1,2,3,4-tetrahydro-2,3,8-trihydroxy-6-methoxy-3-methyl-9,10-anthracenedione (1), together with five known anthraquinones (2–6), two known phenylethyl alcohols (7–8) and one known butanamide (9), were isolated from the mangrove-derived fungus Phomopsis sp. PSU-MA214. Their structures were established by spectroscopic evidence. Compound 1 is a rare ethyltetrahydroanthraquinone and exhibited weak cytotoxicity against breast cancer (MCF-7) cell lines and antibacterial activity against the standard Staphylococcus aureus ATCC25923 and methicillin-resistant S. aureus SK1.     

Pretrichodermamide C and N-methylpretrichodermamide B,two new cytotoxic epidithiodiketopiperazines from hyper saline lake derived Penicillium sp.

Two new epidithiodiketopiperazines, pretrichodermamide C (1) and N-methylpretrichodermamide B (2) were isolated from the fungus Penicillium sp., derived from the sediment of a hyper saline lake located at Wadi El-Natrun in Egypt. The structures of 1 and 2 were unambiguously determined on the basis of one- and two-dimensional NMR spectroscopy and by high-resolution mass spectrometry, as well as by comparison with the literature. Compound 2 showed pronounced cytotoxicity against the murine lymphoma L5178Y cell line with an IC₅₀ value of 2 μM.     

Sesquiterpenes from Curcuma zedoaria rhizomes and their cytotoxicity against human gastric cancer AGS cells

Curcuma zedoaria rhizome (Zingiberaceae) is a well-known traditional medicinal plant used in Ayurvedic and traditional Chinese medicine to treat various cancers. This study aimed to identify the cytotoxic components from C. zedoaria rhizomes that act against gastric cancer, which is the third leading cause of death from cancer worldwide because the MeOH extract of C. zedoaria rhizome was found to show a cytotoxic effect against gastric cancer AGS cells. Repeated column chromatography and semi-preparative HPLC purification were used to separate the components from the C. zedoaria MeOH extract. Two new sesquiterpenes, curcumenol-9,10-epoxide (1) and curcuzedoalide B (2), and 12 known related sesquiterpenes (3–14) were isolated from the C. zedoaria MeOH extract. The structures of new compounds were determined by 1D and 2D NMR spectroscopic experiments and HR-ESIMS, and quantum chemical ECD calculations. The cytotoxic effects of the isolated compounds were measured in human gastric cancer AGS cells using an MTT cell viability assay. Compounds 9, 10, and 12 exhibited cytotoxic effects against gastric cancer AGS cells, with IC₅₀ values in the range of 212–392 μM. These findings provide further experimental scientific evidence to support the traditional use of C. zedoaria rhizomes for the treatment of cancer. Curcumenol (9), 4,8-dioxo-6β-methoxy-7α,11-epoxycarabrane (10), and zedoarofuran (12) were identified as the main cytotoxic components in C. zedoaria rhizomes.     

Antibacterial and anti-phytopathogenic substances from the insect pathogenic fungus Gibellula sp. BCC36964

Four new compounds (1–4), which were (−)-(7R)-7-O-methylsydonic acid, gibellulic acid, gibellulins A and B, together with 14 known compounds (5–17 and orcinol) were isolated from the insect pathogenic fungus, Gibellula sp. BCC36964. The chemical structures were elucidated by employing NMR spectroscopic techniques, physico-chemical data, and chemical method. These compounds were evaluated for the biological activities including anti-bacterial, anti-phytopathogenic, anti-Herpes simplex virus-type 1 activities, and cytotoxicity against both cancerous (MCF-7, KB, NCI-H187) and non-cancerous (Vero) cells.     

Separation and purification of bioactive botrallin and TMC-264 by a combination of HSCCC and semi-preparative HPLC from endophytic fungus Hyalodendriella sp. Ponipodef12

Two dibenzo-α-pyrones, botrallin (1) and TMC-264 (2) were preparatively separated from crude ethyl acetate extract of the endophytic fungus Hyalodendriella sp. Ponipodef12, which was isolated from the hybrid ‘Neva’ of Populus deltoides Marsh × P. nigra L. using a combination of high-speed counter-current chromatography (HSCCC) and semi-preparative HPLC. Botrallin (1) with 74.73 % of purity and TMC-264 (2) with 82.29 % of purity were obtained through HSCCC by employing a solvent system containing n-hexane–ethyl acetate–methanol–water at a volume ratio of 1.2:1.0:0.9:1.0. It was the first time for TMC-264 (2) to be isolated from this fungus. TMC-264 (2) showed strong antimicrobial and antinematodal activity, and botrallin (1) exhibited moderate inhibitory activity on acetylcholinesterase.     

Oxirapentyns B–D produced by a marine sediment-derived fungus Isaria felina (DC.) Fr

Three new highly oxygenated chromene derivatives, oxirapentyns B–D (1–3) and one known oxirapentyn A (4) were isolated from the lipophilic extract of the marine-derived fungus Isaria felina KMM 4639. The structures of compounds 1–3 were determined based on spectroscopic methods. The absolute configuration of oxirapentyn B (1) as 2R, 4S, 5S, 6S, 7R, 8S, 9S was established by a combination of modified Mosher's method, X-ray analysis, and NOESY data. Oxirapentyn A (4) showed weak cytotoxicity against SK-Mel-5, SK-Mel-28 human malignant melanoma, and T-47D human breast cancer cell lines.     

A dimeric pyrrocidine from Neonectria ramulariae is an inhibitor of prolyl oligopeptidase

Four novel alkaloids, bispyrrocidine (5), the epoxy derivative of pyrrocidine B (6), 19-O-methyl-pyrrrocidine B (7) and 19-O-ethyl-pyrrrocidine B (8) were isolated from the endophytic fungus Neonectria ramulariae Wollenw KS-246. Their structures were elucidated using 1D- and 2D-NMR spectroscopy. Compound 6 exhibited cytotoxicity against HL60 cells (IC₅₀ 4.6 μM), whereas 5 showed specific inhibitory activity against prolyl oligopeptidase (IC₅₀ 2.6 μM) in a non-competitive manner.     

An epigenetic modifier enhances the production of anti-diabetic and anti-inflammatory sesquiterpenoids from Aspergillus sydowii

The addition of a DNA methyltransferase inhibitor, 5-azacytidine, to Aspergillus sydowii fungus culture broth changed its secondary metabolites profile. Analysis of the culture broth extract led to the isolation of three new bisabolane-type sesquiterpenoids: (7S)-(+)-7-O-methylsydonol (1), (7S,11S)-(+)-12-hydroxysydonic acid (2) and 7-deoxy-7,14-didehydrosydonol (3), along with eight known compounds. The isolated compounds were evaluated for their anti-diabetic and anti-inflammatory activities. Among the isolates, (S)-(+)-sydonol (4) did not only potentiate insulin-stimulated glucose consumption but also prevented lipid accumulation in 3T3-L1 adipocytes. Additionally, (S)-(+)-sydonol (4) exhibited significant anti-inflammatory activity through inhibiting superoxide anion generation and elastase release by fMLP/CB-induced human neutrophils. This is the first report on isolating a secondary metabolite with anti-diabetic and anti-inflammatory activities from microorganisms.     

New secondary metabolites from the mangrove-derived fungus Aspergillus sp. AV-2

Chemical investigation of the mangrove-derived fungus Aspergillus sp. AV-2 following fermentation on solid rice medium led to the isolation of a new phenyl pyridazine derivative (1) and a new prenylated benzaldehyde derivative, dioxoauroglaucin (2), together with fourteen known compounds (3-16). Chemical structures of the new compounds were unambiguously determined based on HRESIMS and extensive 1D and 2D NMR spectroscopic analyses. Compounds 2-7, 8 and 13 were assessed for their antiproliferative activity against Caco-2 cell lines, where flavoglaucin (6) revealed the most potent cytotoxicity with IC₅₀ of 2.87 μM.     

Indanone and mellein derivatives from the Garcinia-derived fungus Xylaria sp. PSU-G12

Two new compounds, one indanone (1) and one mellein (2), along with 3-hydroxy-4-methyl-1-indanone (3), griseofulvin (4), dechlorogriseofulvin (5), cytochalasin D (6) and three mellein derivatives (7–9) were isolated from the broth extract of the Garcinia-derived fungus Xylaria sp. PSU-G12. The structures were elucidated by spectroscopic analysis. This is the first report on the isolation of indanone derivatives from the genus Xylaria. The isolated compounds were evaluated for antioxidant activity in DPPH assay.     

Synthesis and biological evaluation of amino analogs of Ludartin: Potent and selective cytotoxic agents

Diverse amino analogs of Ludartin, a cytotoxic guaianolide and a position isomer of an anticancer drug, Arglabin were prepared through Michael type addition at its highly active α-methylene-γ-lactone motif. The semisynthetic derivatives were subjected to sulphorhodamine B cytotoxicity assay against a panel of four different human cancer cell lines viz. lung (A-549), leukemia (THP-1), prostate (PC-3) and colon (HCT-116) to look into structure–activity relationship. Few of the analogs displayed potent selective cytotoxicity compared to the parent molecule-Ludartin (1). (11R)-13-(Diethyl amine)-11,13-dihydroludartin (6) and (11R)-13-(piperidine)-11,13-dihydroludartin (10) showed almost same cytotoxicity against leukemia cell lines (THP-1) as that of parent molecule-Ludartin, but were more active against colon (HCT-116) cancer cells. (11R)-13-(Morpholine)-11,13-dihydroludartin (11) displayed selectively better cytotoxicity against Leukemia cancer cells (THP-1) exhibiting IC₅₀ of 2.8 μM. (11R)-13-(6-Nitroindazole)-11,13-dihydroludartin (17) was four times more potent than Ludartin with selective cytotoxic effects against prostate cancer cells (2.2 μM) while as (11R)-13-(6-nitroindazole)-11,13-dihydroludartin (18) exhibited three-fold selective cytotoxicity for Lung (A-549) cancer cell lines exhibiting IC₅₀ of 2.6 μM.     

Secondary metabolites and cytotoxic activities from the endophytic fungus Annulohypoxylon squamulosum

One new dihydrobenzofuran-2,4-dione derivative, designated as annulosquamulin (1), together with 10 known compounds (2–11), were isolated from the n-BuOH-soluble fraction of the 95% EtOH extract of long-grain rice fermented with the endophytic fungus Annulohypoxylon squamulosum BCRC 34022, derived from the stem bark of medicinal plant Cinnamomum sp. Annulosquamulin (1) comprises one dihydrobenzofuran-2,4-dione skeleton, 1-hydroxydecyl side chain, and one γ-lactone ring. Their structures were elucidated by means of spectroscopic and mass-spectrometric analyses, particularly 1D and 2D NMR spectroscopy as well as HRESIMS. All known isolates except 11, were isolated for the first time from this species. In addition, isolated compounds (1–5) were evaluated for their cytotoxicity against the MCF-7, NCI-H460 and SF-268 cell lines using the MTT assay.     

Microbiological transformation of diosgenin by resting cells of filamentous fungus,Cunninghamella echinulata CGMCC 3.2716

Microbial transformation of the steroidal sapogenin diosgenin (1) by resting cells of the filamentous fungus, Cunninghamella echinulata CGMCC 3.2716 was studied. Four metabolites were isolated and unambiguously characterized as (25R)-spirost-5-ene-3β,7β-diol-11-one (2), (25R)-spirost-5-ene-3β,7β-diol (3), (25R)-spirost-5-ene-3β,7β,11α-triol (4), and (25R)-spirost-5-ene-3β,7β,12β-triol (5), by various spectroscopic methods (¹H, ¹³C NMR, DEPT, ¹H–¹H COSY, HMBC, HSQC and NOESY). Compound 2 is a new metabolite. The NMR data and full assignment for the known metabolites (25R)-spirost-5-ene-3β,7β-diol (3) and (25R)-spirost-5-ene-3β,7β,11α-triol (4) are described here for the first time. The biotransformation characteristics observed included were C-7β, C-11α and C-12β hydroxylations. Compounds 1–5 exhibited no significant cytotoxic activity to human glioma cell line U87.