Chemical constituents of the marine-derived fungus Acremonium sp. AN-13.

Two new compounds named 3(S)-hydroxy-1-(2,4,5-trihydroxy-3,6- dimethylphenyl)-hex-4E-en-1-one (1) and acremonilactone (2), together with nine known compounds (3-11), were isolated from the fermentation broth of Acremonium sp. associated with marine sediments collected from South China Sea. NMR and HRESIMS spectroscopic analysis elucidated the structure of two new compounds. Compound 2 had characteristic rotary gate shape skeleton with a six-membered lactone. Compounds 1 and 9 showed DPPH radical scavenging activity with inhibition rates of 96.50 and 85.95% at the concentration of 0.5 mg/ml, respectively. Moreover, compounds 4, 6 and 11 showed definite antibacterial activity against Staphylococcus aureus ATCC 6538.

Hexahydroazulene-2(1H)-one Sesquiterpenoids with Bridged Cyclobutane, Oxetane, and Tetrahydrofuran Rings from the Stems of Daphne papyracea with α-Glycosidase Inhibitory Activity.

Chemical investigation of an alcoholic extract from the stem of Daphne papyracea ("Xuehuagou") led to the isolation of the tetracyclic sesquiterpenoid daphnepapytone A (1), containing a unique caged skeleton with a cyclobutane ring having three tetrasubstituted chirality centers. Also isolated were new guaiane sesquiterpenoids, namely, daphnepapytones B-H (2-8), and one 1,5-diphenylpentanone 2-hydroxy-5-oxo-daphneone (9), together with 26 known compounds. The cyclic metabolites share a 5-isoprenyl-hexahydroazulene-2(1H)-one skeleton with different substitution patterns and a bridged cyclobutane, oxetane, or tetrahydrofuran ring. The planar structures and relative configuration of the new compounds were elucidated on the basis of spectroscopic analysis aided by DFT 13C NMR calculations. The absolute configurations of 1-7 were determined by X-ray single-crystal diffraction or TDDFT-ECD calculations. Daphnepapytones A and C (1 and 3), 2-hydroxy-5-oxodaphneone (9), daphnenone (10), daphneone (11), and 3-methyldaphneolone (12) showed α-glycosidase inhibitory activity, with IC50 values of 159.0, 102.3, 139.3, 43.3, 145.0, and 126.1 µM, respectively.

Asperpenes D and E from the fungus Aspergillus sp. SCS-KFD66 isolated from a bivalve mollusk, Sanguinolaria chinensis.

Two new compounds named asperpenes D (1) and E (2) were isolated from the marine-derived fungus Aspergillus sp. SCS-KFD66. Their structures were determined on the basis of spectroscopic methods. Compound 2 represents the first natural product bearing a 2-substituted-5-oxo-4-phenyl-2,5-dihydrofuran-3-carboxylic acid skeleton. All the compounds were tested for enzyme inhibitory activity against AChE and α-glucosidase and DPPH radical scavenging activity, respectively. [Formula: see text].

Two new indole-diterpenoids from the marine-derived fungus Penicillium sp. KFD28.

Two new compounds named epipaxilline (1) and penerpene J (2) were isolated from the marine-derived fungus Penicillium sp. KFD28. Their structures including absolute configurations were determined on the basis of spectroscopic methods and ECD analysis. Compounds 1 and 2 showed inhibitory activities against PTP1B with IC50 values of 31.5 and 9.5 µM, respectively, and compound 2 also showed inhibitory activities against TCPTP with IC50 value of 14.7 µM.

Zizaane-Type Sesquiterpenoids and Their Rearranged Derivatives from Agarwood of an Aquilaria Plant.

Nine new sesquiterpenoids (1-9) were isolated from ethyl ether extract of agarwood originated from Aquilaria sp., including three novel sesquiterpenoids (1-3) derived from zizaane, together with six zizaane-type sesquiterpenoids (4-9). All structures were unambiguously elucidated based on 1D and 2D NMR spectra as well as by HRESIMS data. The absolute configuration of sesquiterpenoids was determined by comparison of the experimental and computed ECD spectra. In vitro anti-inflammatory assessment showed that compound 9 exhibited inhibition of NO production in LPS-stimulated RAW264.7 cells with an IC50 value of 62.22 ± 1.27 µM.

The Characteristic Fragrant Sesquiterpenes and 2-(2-Phenylethyl)chromones in Wild and Cultivated "Qi-Nan" Agarwood.

Recently, cultivated "Qi-Nan" (CQN) agarwood has emerged as a new high-quality agarwood in the agarwood market owing to its similar characteristics, such as high content of resin and richness in two 2-(2-phenylethyl)chromone derivatives, 2-(2-phenylethyl)chromone (59) and 2-[2-(4-methoxyphenyl)ethyl]chromone (60), to the wild harvested "Qi-Nan" (WQN) agarwood. In this study, we compared the chemical constituents and fragrant components of two types of WQN agarwood from A. agallocha Roxb. and A. sinensis, respectively, with CQN agarwood and ordinary agarwood varieties. Additionally, we analyzed different samples of WQN agarwood and CQN agarwood by GC-MS, which revealed several noteworthy differences between WQN and CQN agarwood. The chemical diversity of WQN was greater than that of CQN agarwood. The content of (59) and (60) was higher in CQN agarwood than in WQN agarwood. For the sesquiterpenes, the richness and diversity of sesquiterpenes in WQN agarwood, particularly guaiane and agarofuran sesquiterpenes, were higher than those in CQN. Moreover, guaiane-furans sesquiterpenes were only detected by GC-MS in WQN agarwood of A. sinensis and could be a chemical marker for the WQN agarwood of A. sinensis. In addition, we summarized the odor descriptions of the constituents and established the correlation of scents and chemical constituents in the agarwood.

Quinazoline-Containing Indole Alkaloids from the Marine-Derived Fungus Aspergillus sp. HNMF114.

Seven new quinazoline-containing indole alkaloids (1-7) named aspertoryadins A-G, along with nine known ones (8-16), were isolated from the marine-derived fungus Aspergillus sp. HNMF114 from the bivalve mollusk Sanguinolaria chinensis. The structures of the new compounds were elucidated from spectroscopic data, X-ray diffraction analysis, ECD spectra analysis, and ECD calculations. Compound 1 bears an aminosulfonyl group in the structure, which is rarely encountered in natural products. Compounds 6, 7, and 13 exhibited quorum sensing inhibitory activity against Chromobacterium violaceum CV026 with MIC values of 32, 32, and 16 µg/well, respectively.

Indole-Diterpenoids with Protein Tyrosine Phosphatase Inhibitory Activities from the Marine-Derived Fungus Penicillium sp. KFD28.

Five new indole-terpenoids named penerpenes E-I (1-5), along with seven known ones (6-12), were isolated from the marine-derived fungus Penicillium sp. KFD28 from a bivalve mollusk, Meretrix lusoria. The structures of the new compounds were elucidated from spectroscopic data and ECD spectroscopic analyses. Compound 1 was assigned as an indole-diterpenoid with a unique 6/5/5/6/6/5/5 heptacyclic ring system. Compound 2 represents an indole-diterpenoid with a new carbon skeleton derived from paxilline by the loss of three carbons (C-23/24/25). Compound 3 contains an additional oxygen atom between C-21 and C-22 compared to paxilline to form an unusual 6/5/5/6/6/7 hexacyclic ring system bearing a 1,3-dioxepane ring, which is rarely encountered in natural products. Compounds 1, 2, 4, and 6 showed inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 14, 27, 23, and 13 µM, respectively.

Sesquiterpenoids and 2-(2-phenylethyl)chromones respectively acting as α-glucosidase and tyrosinase inhibitors from agarwood of an Aquilaria plant.

The ethyl ether extract of agarwood from an Aquilaria plant afforded six new sesquiterpenoids, Agarozizanol A - F (1-6), together with four known sesquiterpenoids and six known 2-(2-phenylethyl)chromones. Their structures were elucidated via detailed spectroscopic analysis, X-ray diffraction, and comparisons with the published data. All the isolates were evaluated for the α-glucosidase and tyrosinase inhibitory activities in vitro. Compounds 5, 7, 8, and 10 showed significant inhibition of α-glucosidase with IC50 values ranging between 112.3 ± 4.5 and 524.5 ± 2.7 µM (acarbose, 743. 4 ± 3.3 µM). Compounds 13 and 14 exhibited tyrosinase inhibitory effect with IC50 values of 89.0 ± 1.7 and 51.5 ± 0.6 µM, respectively (kojic acid, 46.1 ± 1.3). In the kinetic studies, compounds 5 and 14 were found to be uncompetitive inhibitors for α-glucosidase and mixed type inhibitors for tyrosinase, respectively. Furthermore, molecular docking simulations revealed the binding sites and interactions of the most active compounds with α-glucosidase and tyrosinase.

Helvolic Acid Derivatives with Antibacterial Activities against Streptococcus agalactiae from the Marine-Derived Fungus Aspergillus fumigatus HNMF0047.

Streptococcus agalactiae is a hazardous pathogen that can cause great harm to humans and fish. In the present study, the known fungal metabolite helvolic acid (10), seven new helvolic acid derivatives named 16- O-deacetylhelvolic acid 21,16-lactone (2), 6- O-propionyl-6,16- O-dideacetylhelvolic acid 21,16-lactone (3), 1,2-dihydro-6,16- O-dideacetylhelvolic acid 21,16-lactone (4), 1,2-dihydro-16- O-deacetylhelvolic acid 21,16-lactone (5), 16- O-propionyl-16- O-deacetylhelvolic acid (6), 6- O-propionyl-6- O-deacetylhelvolic acid (7), and 24- epi-6ß,16ß-diacetoxy-25-hydroxy-3,7-dioxo-29-nordammara-1,17(20)-diene-21,24-lactone (9), and two known ones (1 and 8) were isolated from the marine-derived fungus Aspergillus fumigatus HNMF0047 obtained from an unidentified sponge from Wenchang Beach, Hainan Province, China. The structures and the absolute configurations of the new compounds were unambiguously elucidated by spectroscopic data and electronic circular dichroism (ECD) spectroscopic analyses along with quantum ECD calculations. In addition, the spectroscopic data of compound 1 are reported here for the first time, the configuration of C-24 of known compound 8 was revised based on comparison of its ROESY data with its C-24 epimer 9, and the absolute configuration of 8 was also determined for the first time. Compounds 6, 7, and 10 showed stronger antibacterial activity than a tobramycin control against S. agalactiae with MIC values of 16, 2, and 8 µg/mL, respectively.

Chemical Constituents of the Marine-Derived Fungus Aspergillus sp. SCS-KFD66.

Five new compounds named asperpenes A-C (1⁻3), 12,13-dedihydroversiol (4), and methyl 6-oxo-3,6-dihydro-2H-pyran-4-carboxylate (5), along with 10 known compounds (6⁻15), were isolated from the fermentation broth of Aspergillus sp. SCS-KFD66 associated with a bivalve mollusk, Sanguinolaria chinensis, collected from Haikou Bay, China. The structures of the compounds, including the absolute configurations of their stereogenic carbons, were unambiguously determined by spectroscopic data, single-crystal X-ray diffraction analysis, and electronic circular dichroism (ECD) spectral analysis, along with quantum ECD calculations. The growth inhibitory activity of the compounds against four pathogenic bacterial (Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 6538, Listeria monocytogenes ATCC 1911, and Bacillus subtilis ATCC 6633), their enzyme inhibitory activities against acetylcholinesterase and α-glucosidase, and their DPPH radical scavenging activity were evaluated.

Two new 2-(2-Hydroxy-2-phenylethyl)chromens from agarwood originating from Aquilaria crassna.

Two new 2-(2-hydroxy-2-phenylethyl)chromones (1‒2), along with three known 2-(2-phenylethyl)chromones (3‒5), were isolated from the agarwood originating from Aquilaria crassna Pierre ex Lecomte. Their structures were determined by the spectroscopic methods including 1D and 2D NMR analysis and comparison with reported data in the literature. All the compounds were isolated from agarwood of A. crassna for the first time. Compounds 1 and 2 exhibited inhibitory activity against acetylcholinesterase (AChE) with 17.4 ± 0.6 and 15.8 ± 0.7%, respectively, at a concentration of 50 µg/ml. Besides, Compound 3 expressed antibacterial activities against Ralstonia solanacearum with diameter of the inhibition zone of 6.80 ± 0.08 mm at a concentration of 10 mg/ml.

Chrodrimanins K-N and Related Meroterpenoids from the Fungus Penicillium sp. SCS-KFD09 Isolated from a Marine Worm, Sipunculus nudus.

Six new meroterpenoids, chrodrimanins K-N (1-4), including two uncommon chlorinated ones (1 and 2), and verruculides B2 (5) and B3 (6), as well as seven known ones (7-13), were isolated from the fermentation broth of Penicillium sp. SCS-KFD09 isolated from a marine worm, Sipunculus nudus, from Haikou Bay, China. The structures including the absolute configurations of the new compounds were unambiguously elucidated by spectroscopic data, X-ray diffraction analysis, and ECD spectra analysis along with quantum ECD calculations. In addition, the X-ray crystal structures and absolute configurations of two previously reported meroterpenoids, chrodrimanins F (9) and A (11), are described for the first time. Compounds 1, 4, and 7 displayed anti-H1N1 activity with IC50 values of 74, 58, and 34 µM, respectively, while compound 5 showed weak inhibitory activity against Staphylococcus aureus with an MIC of 32 µg/mL.

A new apotirucallane-type triterpenoid from Atalantia buxifolia.

A new triterpenoid (1) with apotirucallane skeleton was isolated from the ethanol extract of the roots of Atalantia buxifolia (Poir.) Oliv. The complete structural assignment of the new compound was elucidated by a combination of 1D, 2D NMR (HMQC, HMBC, COSY, and NOESY), and HR-ESI-MS analysis. Moreover, this new compound was evaluated in vitro for its cytotoxic, antimicrobial and enzymes inhibitory activities.

Sesquiterpenoids and bibenzyl derivative from Dendrobium hercoglossum.

Three new sesquiterpenoids, dendrohercoglin A - C (1-3), and one new bibenzyl derivative, dendronbiline D (4), together with nine known sesquiterpenoids (5-13) were isolated from Dendrobium hercoglossum. The structures of the new compounds were elucidated by extensive spectroscopic analysis as well as NMR and ECD calculations. All the compounds were evaluated for their neuroprotective and anti-inflammatory activities. Compounds 2 and 3 increased the H2O2-damaged SH-SY5Y cell viabilities from 43.3% to 58.6% and 68.4%, respectively. Compound 4 exhibited pronounced anti-inflammatory activity with IC50 value of 9.5 ± 0.45 µM which was superior to the reference compound quercetin (IC50: 15.7 ± 0.89 µM).

Isolation and biological activity of six new polyketide and terpenoid derivatives from Neopestalotiopsis Clavispora AL01.

A fungus strain, Neopestalotiopsis clavispora AL01, was isolated from the leaf spot of the plant Phoenix dactylifera. Further chemical investigation of the fermentation extract of this strain afforded six new secondary metabolites (1-6), along with 11 known compounds (7-17) which included a new natural compound (7). Their structures were determined by extensive spectroscopic analysis including one-and two-dimensional (1D and 2D) NMR spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), and ECD and NMR calculations. All compounds were evaluated for their phytotoxic activities. Among them, compounds 10, 12 and 13 exhibited phytotoxic activities against Nicotiana tabacum. Compound 3 exhibited weak antibacterial activity against methicillin-resistant Staphylococcus aureus, Micrococcus luteus and Vibrio harveyi. Taken collectively, these findings establish a solid research foundation for future investigations on bioactive natural products derived from phytopathogenic fungi.

Bi-2-(2-phenethyl)chromone derivatives from agarwood of Aquilaria filaria in the Philippines.

Twelve undescribed 2-(2-phenethyl)chromone dimers (1-12) were isolated from EtOAc extract of agarwood originating from Aquilaria filaria in the Philippines, guided by a UHPLC-MS analysis. Their structures were elucidated by 1D NMR, 2D NMR, and HR-ESI-MS spectra. The absolute configuration of 2-(2-phenylethyl)chromone dimers was determined by single-crystal X-ray diffraction analysis and comparison of the experimental and calculated ECD spectra. Compounds 1, 2, 5 and 9-12 exhibited potent to moderate anti-inflammatory activity with IC50 values in the range of 22.43 ± 0.86 to 53.88 ± 4.06 µM.

Dimeric 2-(2-phenethyl)chromones from agarwood of Aquilaria filaria.

Four new 2-(2-phenethyl)chromone dimers (1-4) were isolated from EtOAc extract of agarwood originating from Aquilaria filaria from Philippines. Their structures were elucidated by spectroscopic analysis (1D and 2D NMR, and HRESIMS) and comparison of the experimental and computed ECD curves. Compounds 1-4 exhibited inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with IC50 values in the range from 33.94 to 57.53 µM.

A new picrotoxane-type sesquiterpene from Dendrobium nobile Lindl.

A picrotoxane-type sesquiterpene, dendroterpene E (1), together with five benzene derivatives (2-6), were isolated from the stems of Dendrobium nobile Lindl. Their structures were elucidated by spectroscopic analysis and X-ray diffraction analysis. Compound 1 was a new picrotoxane-type sesquiterpene with a C-9/C-1/O/C-11 oxetane ring, which was first encountered in this type of compounds. Compounds 1-3 exhibited inhibitory activities against α-glycosidase.

LC-MS-guided isolation of 2-(2-phenylethyl)chromone dimers from red soil agarwood of Aquilaria crassna.

Six new 2-(2-phenylethyl)chromone dimers (1-6) were isolated from ethyl ether extract of red soil agarwood of Aquilaria crassna from Vietnam by LC-MS-guided fractionation procedure. Their structures were unambiguously elucidated based on HRESIMS, 1D and 2D NMR spectra. The absolute configuration of 2-(2-phenylethyl)chromone dimers was determined by comparison of the experimental and computed ECD spectra. Compound 6 displayed cytotoxicity against the human myeloid leukemia cell line (K562) with an IC50 value of 39.49 µM.