Four New Polyhydroxy Cyclohexanes from the Stems of Fissistigma tientangense.

Four undescribed polyhydroxy cyclohexanes, fissoxhydrylenes A-D (1-4), together with two known biogenetically related polyhydroxy cyclohexanes (5 and 6) were isolated from the stems of Fissistigma tientangense Tsiang et P. T. Li. Their structures were elucidated by detailed analysis of NMR, HR-ESI-MS, IR, UV and Optical rotations data. The absolute configuration of 1 was confirmed by X-ray crystallographic. The absolute configurations of 2-4 were confirmed by chemical reaction and optical rotations. Compound 4 represent the first example of a no substituent polyhydroxy cyclohexanes from natural products. All isolated compounds were evaluated for their anti-inflammatory activities against the lipopolysaccharide-induced nitric oxide (NO) production in mouse macrophage RAW 264.7 cells in vitro. Compounds 3 and 4 showed inhibitory activities with the IC50 values of 16.63±0.06 µM and 14.38±0.08 µM, respectively.

Three new long-chain polyenes from the mangrove-derived fungus Penicillium herquei JX4.

One new epimer pair of long-chain polyenes penicilqueis E (1) and F (2), and one new long-chain polyene pinophol G (3), along with one known compound (4), were obtained from EtOAc extract of the mangrove-derived fungus Penicillium herquei JX4. Their structures were elucidated by detailed analysis of comprehensive spectroscopic data. The inhibitory activities of all compounds against the nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro were evaluated.

Oxalierpenes A and B, Unusual Indole-Diterpenoid Derivatives with Antiviral Activity from a Marine-Derived Strain of the Fungus Penicillium oxalicum.

Oxalierpenes A and B (1 and 2), two unusual indole-diterpenoid derivatives, were obtained from the marine-derived fungus Penicillium oxalicum. The absolute configurations of 1 and 2 were elucidated by calculated TDDFT ECD and DP4plus methods. Oxalierpene A (1) represents the first indole-diterpenoid derivative with a five-membered ring of 4-hydroxy-5,5-dimethyldihydrofuran-3-one as a side chain. Oxalierpene B (2) has a unique 6/5/6/5/5/6/6/5/5 ring system. Compounds 1 and 2 showed antiviral activity against the H1N1 virus and respiratory syncytial virus (RSV), with IC50 values ranging from 2.8 to 9.4 µM.

Talaromarins A-F: Six New Isocoumarins from Mangrove-Derived Fungus Talaromyces flavus TGGP35.

Six new isocoumarin derivative talaromarins A-F (1-6), along with 17 known analogues (7-23), were isolated from the mangrove-derived fungus Talaromyces flavus (Eurotiales: Trichocomaceae) TGGP35. Their structures were identified by detailed IR, UV, 1D/2D NMR and HR-ESI-MS spectra. The absolute configurations of new compounds were determined by the modified Mosher's method and a comparison of their CD spectra with dihydroisocoumarins described in the literature. The antioxidant, antibacterial, anti-phytopathogenic and inhibitory activity against α-glucosidase of all the isolated compounds were tested. Compounds 6-11, 17-19 and 21-22 showed similar or better antioxidant activity than the IC50 values ranging from 0.009 to 0.27 mM, compared with the positive control trolox (IC50 = 0.29 mM). Compounds 10, 18, 21 and 23 exhibited strong inhibitory activities against α-glucosidase with IC50 values ranging from 0.10 to 0.62 mM, while the positive control acarbose had an IC50 value of 0.5 mM. All compounds showed no antibacterial or anti-phytopathogenic activity at the concentrations of 50 µg/mL and 1 mg/mL, respectively. These results indicated that isocoumarins will be useful to developing antioxidants and as diabetes control agents.

Design, Semisynthesis, Insecticidal and Antibacterial Activities of a Series of Marine-Derived Geodin Derivatives and Their Preliminary Structure-Activity Relationships.

To enhance the biological activity of the natural product geodin (1), isolated from the marine-derived fungus Aspergillus sp., a series of new ether derivatives (2-37) was designed and semisynthesized using a high-yielding one-step reaction. In addition, the insecticidal and antibacterial activities of all geodin congeners were evaluated systematically. Most of these derivatives showed better insecticidal activities against Helicoverpa armigera Hübner than 1. In particular, 15 showed potent insecticidal activity with an IC50 value of 89 µM, comparable to the positive control azadirachtin (IC50 = 70 µM). Additionally, 5, 12, 13, 16, 30 and 33 showed strong antibacterial activity against Staphylococcus aureus and Aeromonas salmonicida with MIC values in the range of 1.15-4.93 µM. The preliminary structure-activity relationships indicated that the introduction of halogenated benzyl especially fluorobenzyl, into 1 and substitution of 4-OH could be key factors in increasing the insecticidal and antibacterial activities of geodin.

A new bioactive isocoumarin from the mangrove-derived fungus Penicillium sp. TGM112.

A new isocoumarin, penicimarin N (1), along with five known compounds (2-6), were isolated from the mangrove-derived fungus Penicillium sp. TGM112. The structure of 1 was elucidated on the basis of extensive spectroscopic data analysis, and the absolute configuration of 1 was determined by comparison of their circular dichroism (CD) spectra with the literature. The structures of known compounds were determined by comparison with the literature data. All the isolated compounds were examined for their antioxidant and α-glucosidase activities. Compound 1 showed strong antioxidant activity with the IC50 value of 1.0 mM, and 1 also exhibited moderate inhibitory activity against α-glucosidase with the IC50 value of 620 µM.

Austins-Type Meroterpenoids from a Mangrove-Derived Penicillium sp.

Three unusual austins-type meroterpenoids penicianstinoids C-E (1-3) were obtained from the mangrove-derived fungus Penicillium sp. TGM112. The structures of 1-3 including absolute configurations were determined by detailed NMR, MS spectroscopic data, X-ray diffraction analysis, and calculated electronic circular dichroism data. Penicianstinoid C (1) was the first austins-type meroterpenoid with a unique 6/6/6/5 rearranged tetracyclic skeleton possessing two unusual spirocyclic moieties (2-oxaspiro[5.5]undeca-4,7-dien-3-one and 6-methylene-2-oxaspiro[4.5]decane-1,4-dione). Penicianstinoid D (2) was an unusual austins-type meroterpenoid with a 6/6/6/6 tetracyclic skeleton containing an octahydro-2H-chromen-2-one unit. Penicianstinoid E (3) possessed a 6/5/6/6/6/5 fused hexacyclic skeleton with an uncommon five-membered ether ring system. The plausible biosynthetic pathway of 1-3 is also proposed. Compounds 1 and 3 inhibited the growth of newly hatched Helicoverpa armigera Hubner larvae with IC50 values of 100 and 200 µg/mL, respectively.

Three new methylated Δ8-pregnene steroids from the Polyalthia laui-derived fungus Stemphylium sp. AZGP4-2.

Three new methylated Δ8-pregnene steroids, stemphylisteroids A-C (1-3) were isolated from the medicinal plant Polyalthia laui-derived fungus Stemphylium sp. AZGP4-2. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. The absolute configuration of 1 was determined by X-ray crystallographic analysis. Compound 1 show antibacterial activity against Escherichia coli with the MIC value of 6.25 µg/mL, and 2 exhibited a broad spectrum of antibacterial activities against six pathogenic bacteria with the MIC values ranging from 12.5 to 50 µg/mL. The discovery of three methylated Δ8-pregnene steroids 1-3 are a further addition to diverse and complex array of methylated steroids.

Four New Chromone Derivatives from Colletotrichum gloeosporioides.

Four previously unreported chromones, 5-hydroxy-2-(hydroxymethyl)-8-methoxy-4H-chromen-4-one (1), (5R,7S)-5,7-dihydroxy-2-propyl-5,6,7,8-tetrahydro-4H-chromen-4-one (2), (5R,7S)-5,7-dihydroxy-2-methyl-5,6,7,8-tetrahydro-4H-chromen-4-one (3), and (5R,7S)-5,7-dihydroxy-2-[(E)-prop-1-en-1-yl]-5,6,7,8-tetrahydro-4H-chromen-4-one (4), as well as one known analogue 5-hydroxy-2-methyl-4H-chromen-4-one (5) were isolated from the fermentation broth of the endophytic fungus Colletotrichum gloeosporioides derived from the mangrove Ceriops tagal. Their structures were elucidated based on extensive spectroscopic analyses. The absolute configurations of 2-4 were determined by comparison the experimental and calculated electronic circular dichroism (ECD) spectra. Compound 2 showed cytotoxic activity against A549 cell line with the IC50 value of 0.094 mm.

Bioactive Polyketide Derivatives from the Mangrove-Derived Fungus Daldinia eschscholtzii HJ004.

Five new tetralones, daldiniones A-E (1-5), three new chromones, 7-hydroxy-5-methoxy-2,3-dimethylchromone (9), 5-methoxy-2-propylchromone (10), and 7-ethyl-8-hydroxy-6-methoxy-2,3-dimethylchromone (11), and two new lactones, helicascolides D and E (16 and 17), together with nine known metabolites (6-8, 12-15, and 18-19) were isolated from the mangrove-derived fungus Daldinia eschscholtzii HJ004. The structures and absolute configurations of the new compounds were determined by analyzing MS and NMR data and utilizing GIAO based 13C NMR chemical shift calculations and quantum chemical electronic circular dichroism (ECD) calculations. Compounds 9, 13, and 18 showed inhibitory activities against α-glucosidase with IC50 values of 13, 15, and 16 µM, respectively.

Bioactive Meroterpenoids and Isocoumarins from the Mangrove-Derived Fungus Penicillium sp. TGM112.

Two new meroterpenoids, penicianstinoids A and B (1 and 2), and eight new isocoumarins, peniciisocoumarins A-H (3-10), together with 10 known analogues (11-20) were obtained from the mangrove-derived fungus Penicillium sp. TGM112. The structures and absolute configurations of 1-10 were determined by interpretation of detailed NMR, MS spectroscopic data, X-ray diffraction analyses, modified Mosher's method, and calculated electronic circular dichroism data. Compounds 1-4, 7, 8, 10, 12, 13, and 16 showed growth inhibition activity against newly hatched larvae of Helicoverpa armigera Hubner with IC50 values ranging from 50 to 200 µg/mL, respectively. Compounds 1, 2, and 11-15 displayed activity against Caenorhabditis elegans with EC50 values ranging from 9.4 (± 1.0) to 38.2 (± 0.6) µg/mL, respectively. Compound 1 represents an austinoid-like meroterpenoid that is reported here for the second time, in which a carbon-carbon double bond was oxidized to a carbonyl group at C-1'-C-2'.

3,4- seco-Norclerodane Diterpenoids from the Roots of Polyalthia laui.

Ten new clerodane diterpenoids, polylauioids A-J (1-10), and five known analogues (11-15) were isolated from the roots of Polyalthia laui. Among the new compounds, 3 and 8 are artifacts. The structures were elucidated using spectroscopic methods and by comparison with published NMR spectroscopic data. The absolute configurations of 4, 5, and 7 were defined based on single-crystal X-ray diffraction and electronic circular dichroism data. Compounds 1 and 2 represent the first examples of rearranged 3,4- seco-norclerodane diterpenoids, and a putative biosynthesis pathway for these compounds is proposed. Compounds 1, 4, 6, 7, 9, and 10 showed anti-HIV activities with EC50 values ranging from 12.2 to 35.2 µM.

Bioactive cytosporone derivatives isolated from the mangrove-derived fungus Dothiorella sp. ML002.

Three new cytosporone derivatives dothiorelones K-M (1, 2 and 7), together with six known ones (3-6, 8 and 9) were isolated from the mangrove-derived fungus Dothiorella sp. ML002. Their structures were determined by comprehensive 1D, 2D NMR spectroscopic and HR-ESI-MS spectroscopic data. Compounds 1, 2 and 5 displayed inhibitory activities against α-glucosidase with the IC50 values of 22.0, 77.9 and 5.4 µg/mL, respectively. Additionally, compounds 1, 2, and 5 also exhibited antibacterial activities against Staphylococcus aureus (ATCC 6538) with the same MIC values of 50 µg/mL, respectively. The results indicated that cytosporone derivatives will be useful to as diabetes control agents.

Bioactive Secondary Metabolites from the Culture of the Mangrove-Derived Fungus Daldinia eschscholtzii HJ004.

Two new polyketides, 8-O-methylnodulisporin F (1) and nodulisporin H (2), two new naphthoquinones, 5-hydroxy-2-methoxy-6,7-dimethyl-1,4-naphthoquinone (3) and 5-hydroxy-2-methoxynaphtho[9-c]furan-1,4-dione (4), and a new naphthofuran 1,3,8-trimethoxynaphtho[9-c]furan (5), along with five known compounds 4-O-methyl eleutherol (6), 2-acetyl-7-methoxybenzofuran (7), (-)-orthosporin (8), diaporthin (9), and 6-hydroxymellein (10), were obtained from the EtOAc extract of the mangrove-derived fungus Daldinia eschscholtzii HJ004. The structures of the isolated compounds were elucidated by extensive NMR and MS analyses, while the absolute configurations of the stereogenic carbons were established based on experimental and calculated electronic circular dichroism spectra. Compounds 4 and 7 displayed a potent inhibitory activity against α-glucosidase with the IC50 values of 5.7 and 1.1 µg/mL, respectively. Compounds 1 and 2 showed a moderate antibacterial activity against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA) and Bacillus cereus, with minimum inhibitory concentration (MIC) values ranging from 6.25 to 12.5 µg/mL. Compound 3 exhibited antibacterial activity against B. cereus with the MIC value of 12.5 µg/mL.

Four New Insecticidal Xanthene Derivatives from the Mangrove-Derived Fungus Penicillium sp. JY246.

Four new xanthene derivatives, penicixanthenes A-D (1-4), and one known compound 5 were isolated from a marine mangrove endophytic fungus Penicillium sp. JY246 that was obtained from the stem of Ceriops tagal. Their structures were determined by detailed NMR, MS spectroscopic data, modified Mosher's method, and calculated electronic circular dichroism data. All of the isolated compounds were examined for insecticidal activity. Compounds 2 and 3 showed growth inhibition activity against newly hatched larvae of Helicoverpa armigera Hubner with the IC50 values 100 and 200 µg/mL, respectively, and compounds 1, 3, and 4 showed insecticidal activity against newly hatched larvae of Culex quinquefasciatus with LC50 values of 38.5 (±1.16), 11.6 (±0.58), and 20.5 (±1) µg/mL, respectively. The four xanthene derivatives have the potential to be developed as new biopesticides.

Bioactive Lactones from the Mangrove-Derived Fungus Penicillium sp. TGM112.

Three new lactones penicilactones A-C (1-3) were obtained from the mangrove-derived fungus Penicillium sp. TGM112. Their structures and absolute configurations were determined by detailed NMR, MS spectroscopic data, Mo2(OAc)4-induced electronic circular dichroism (ECD), and circular dichroism (CD) spectroscopy. Compound 1 showed antibacterial activity against Staphylococcus aureus with an MIC value of 6.25 µg/mL. Compound 2 showed insecticidal activity against newly hatched larvae of Culex quinquefasciatus with the LC50 value of 78.5 (±0.58) µg/mL.

Penicilindoles A-C, Cytotoxic Indole Diterpenes from the Mangrove-Derived Fungus Eupenicillium sp. HJ002.

Three new indole diterpenes, penicilindoles A-C (1-3), were isolated from the mangrove-derived fungus Eupenicillium sp. HJ002. Their planar structures and absolute configurations were determined by interpretation of NMR spectroscopic data, HR-ESIMS, and X-ray diffraction analysis using Cu Kα radiation. The cytotoxic and antibacterial activities were evaluated in vitro; penicilindole A (1) showed cytotoxic activity against human A549 and HepG2 cell lines with IC50 values of 5.5 and 1.5 µM, respectively.

Guaiane-Type Sesquiterpenoids from Fissistigma oldhamii Inhibit the Proliferation of Synoviocytes.

Three guaiane-type sesquiterpenoids, dysodensiols G-I (1-3), together with five known sesquiterpenoids (4-8) were isolated from the stems of Fissistigma oldhamii (Hemsl.) Merr. Compound 1 represents the first example of an ene(6 → 5)-abeo-14-norguaiane sesquiterpenoid derived from natural products. Their structures were elucidated by a combination of 1D and 2D NMR and MS spectra. The absolute configuration of 2 was determined by an X-ray crystallographic analysis. The inhibitory effect of all compounds on the proliferation of primary synovial cells was evaluated. Compound 3 showed a potent inhibitory effect on the proliferation of synoviocytes with an IC50 value of 1.0 µM.

Bioactive Phenanthrene and Bibenzyl Derivatives from the Stems of Dendrobium nobile.

A new enantiomeric pair of spirodiketones, (+)- and (-)-denobilone A (1 and 2), three new phenanthrene derivatives (3-5), and three new biphenanthrenes (22-24), along with 11 known phenanthrene derivatives (6-16), five known bibenzyl derivatives (17-21), and four known biphenanthrenes (25-28), were isolated from Dendrobium nobile. The structures of 1-5 and 22-24 were elucidated using comprehensive spectroscopic methods. (+)-Denobilone and (-)-denobilone A (1 and 2) were isolated as a pair of enantiomers by chiral HPLC. The absolute configurations of (+)- and (-)-denobilone A (1 and 2) were determined by comparing their experimental and calculated electronic circular dichroism spectra. The absolute configuration of denobilone B (3) was determined by X-ray crystallographic analysis. The inhibitory activities of all compounds against nine phytopathogenic fungi and three cancer cell lines were evaluated.

Dihydroisocoumarins from the Mangrove-Derived Fungus Penicillium citrinum.

Three new dihydroisocoumarin penicimarins G-I (1-3), together with one known dihydroisocoumarin (4) and three known meroterpenoids (5-7), were obtained from a fungus Penicillium citrinum isolated from the mangrove Bruguiera sexangula var. rhynchopetala collected in the South China Sea. Their structures were elucidated by the detailed analysis of spectroscopic data. The absolute configuration of 1 was determined by the X-ray diffraction analysis using Cu Kα radiation. The absolute configurations of 2 and 3 were determined by comparison of their circular dichroism (CD) spectra with the literature. All compounds were evaluated for their antibacterial activities and cytotoxic activities.