Formyl phloroglucinol meroterpenoids from Eucalyptus tereticornis and their bioactivities

Five new formyl phloroglucinol meroterpenoids (FPMs), eucalteretials A?E (1–5), along with eight known analogues (6?13), were isolated from the twigs and leaves of Eucalyptus tereticornis. Their structures were established mainly by analysis of comprehensive spectroscopic data, and their absolute configurations were determined by electron circular dichroism (ECD) calculation. Within FPMs, both 1 and 2 are rare adducts of formyl phloroglucinol moiety and germacrene unit with different coupling patterns, respectively. Compound 3 exhibited significant cytotoxicity against HCT116?cell line with an IC₅₀ value of 4.76?μM. In addition, 5 and 9 were proved to be rare topoisomerase I (Top1) inhibitors.     

Cytotoxic indolocarbazoles alkaloids from the streptomyces sp. A65

Three new indolocarbazoles alkaloids together with nine known compounds were isolated from the rice solid fermentation of the marine-derived Streptomyces sp. A65. Their structures were elucidated by interpretation of spectroscopic and spectrometric data (1D and 2D NMR, IR, and HRESIMS). The absolute configurations of compounds 1 and 2 were determined by single-crystal X-ray crystallographic analysis, and 3 was assigned on the basis of experimental and calculated electronic circular dichroism spectra. All of these compounds were evaluated for cytotoxic activity assay. Compounds 6 and 10 exhibited significant cytotoxicity against PC3 cell lines with IC₅₀ values of 1.96 and 2.92 μM, respectively; Compounds 2 and 3 showed moderate cytotoxic activity with IC₅₀ values of 9.67 and 6.79 μM, respectively. Additionally, compounds 1–4 also were also tested for enzyme inhibition activities of Protein kinase C and Brution tyrosine kinase. They showed moderate activity with IC₅₀ values ranging from 0.25 μM to 1.91 μM except for compound 1, which has no inhibition activity for protein kinase C.     

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.     

Secondary metabolites of the lichen-associated fungus Apiospora montagnei

The endolichenic fungus Apiospora montagnei isolated from the lichen Cladonia sp. was cultured on solid rice medium, yielding the new diterpenoid libertellenone L (1), the new pyridine alkaloid, 23-O-acetyl-N-hydroxyapiosporamide (2) and the new xanthone derivative 8-hydroxy-3-hydroxymethyl-9-oxo-9H-xanthene-1-carboxylic acid methyl ether (3) together with 19 known compounds (4–22). The structures of the new compounds were elucidated by 1D and 2D NMR spectra as well as by HRESIMS data. The absolute configuration of the new 6,7-seco-libertellenone derivative 1 was determined by single-crystal X-ray diffraction. Four additional known compounds 23–26 were isolated when NaCl or NH₄Cl were added to solid rice medium. Compounds 7–9, 18 and 26 exhibited significant cytotoxicity against the L5178 murine lymphoma cell line with IC₅₀ values of 2.6, 0.2, 2.1, 2.7 and 1.7 μM, respectively.     

Cyclic pentapeptide type compounds from Clerodendrum japonicum (Thunb.) Sweet

Two previous undescribed cyclic pentapeptide-type compounds (1–2), with two known ones (3–4), were first isolated and purified from Clerodendrum japonicum (Thunb.) Sweet. Their structures were elucidated by extensive spectroscopic data (1D and 2D NMR) analysis. The absolute configurations of the two compounds were assigned using a combination of Marfey’s method and HPLC-MS analysis. All four compounds showed weak cytotoxicity against four human cancer cells lines (T24, A549, HepG2, MGC-803), with IC₅₀ values ranging from 23.8 to 39.6?μM.     

Diterpenes and sesquiterpenes with anti-Coxsackie virus B3 activity from the stems of Illicium jiadifengpi

Seven new diterpenes, jiadifenoic acids J–P (1–7), two new sesquicarane sesquiterpenes, sesquicaranoic acids A and B (8 and 9), and four known compounds, were isolated from the stems of Illicium jiadifengpi. The trans-fused A/B ring junction in diterpenes was deduced from NMR data analysis and confirmed by single-crystal X-ray crystallography of 3. The absolute configurations of compounds 1 and 5 were determined using the Mo₂(OAc)₄-induced circular dichroism (ICD) method. Compounds 8 and 9 are a pair of C-10 epimers, and their absolute configurations were confirmed by analyzing their CD and ICD data. All of the isolated compounds were evaluated in vitro for their antiviral activities against Coxsackie virus B3 (CVB3). Among the isolated compounds, 4, 5, 7, 10, and 11 exhibited reasonable activity against CVB3, with IC₅₀ values of 7.0–22.2 μmol/mL and selective index values (SI=TC₅₀/IC₅₀) of 49.3, 37.1, 31.3, 45.6 and 40.9, 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.     

Halichonic acid,a new rearranged bisabolene-type sesquiterpene from a marine sponge Halichondria sp.

A new compound, halichonic acid (1), was isolated from a marine sponge Halichondria sp., together with (6R,7S)-7-amino-7,8-dihydro-α-bisabolene (2). The structure of 1 was elucidated by spectroscopic analysis and ECD spectrum calculation to be a rearranged bisabolene-type sesquiterpene having a 3-azabicyclo[3.3.1]nonene moiety. Compound 2 was cytotoxic against HeLa cells with an IC₅₀ value of 50?μM, whereas 1 did not show cytotoxicity even at 50?μM. It is possible that 1 is biosynthesized from farnesyl pyrophosphate and glycine, with rearrangement.     

A novel norsesquiterpene alkaloid from the mushroom-forming fungus Flammulina velutipes

A new norsesquiterpe alkaloid（1） was isolated from the solid culture of mushroom-forming fungus Flammulina velutipes fermented on rice.The structure of 1 was elucidated by spectroscopic methods.The absolute configuration of C-1 in 1 was determined using the circular dichroism data of their [Rh₂（OCOCF₃）₄]complex.     

Thioquinomycins A-D,novel naphthothiophenediones from the marine-derived Streptomyces sp. SS17F

Thioquinomycins A-D (1–4), four novel naphthothiophenediones were isolated from the rice-based medium of the marine-derived Streptomyces sp. SS17F. Their structures were elucidated by spectroscopic methods and HRESIMS data. The absolute configurations of all the compounds were elucidated by X-ray diffraction analysis, ECD and Mosher's method combined with ¹⁹F-NMR. Compounds 1–4 showed moderate cytotoxicity against NCI-H1975 with IC₅₀ values from 17.5 to 50?μM. In addition, compounds 1–4 also exhibited inhibitory activities against PKCα and ROCK2 protein kinase.     

Acylphloroglucinol derivatives from the twigs and leaves of Callistemon salignus

Three new acylphloroglucinol derivatives, callisalignones A–C (1–3), six new meroterpenoids, callisalignenes A–F (4–9), along with 18 known analogues (10–27) were isolated from the twigs and leaves of Callistemon salignus. Their structures and absolute configurations were established by comprehensive spectroscopic evidences (NMR, MS, amd electronic circular dichroism calculations). The absolute configurations of callistenones B (13) and H (14) were determined by comparison of their ECD spectra with that of callisalignone B (2). Callisalignones B and C are new adducts of β-triketone and acylphloroglucinol, whereas callisalignenes A–D are new meroterpenoids of acylphloroglucinol and α-phellandrene with different coupling models via hetero-Diels-Alder reaction, respectively. Myrtucommulone D (15) showed significant antibacterial activity against Staphylococcus aureus and three drug resistant S. aureus strains with MIC values of 1.953 and 0.975 μg/mL, respectively. Isomyrtucommulone B (17) displayed remarkable antibacterial activity against Escherichia coli with an MIC value of 0.122 μg/mL. Cytotoxic assay revealed that isomyrtucommulone B (17) was the most active against HCT116 with an IC₅₀ value of 2.09 ± 0.10 μM.     

Abiestetranes A and B,two unique tetraterpenes from Abies fabri

Abiestetranes A (1) and B (2), two unique tetraterpenes formed by Diels–Alder cycloaddition between a lanostane triterpenoid and a monoterpenoid, were isolated from Abies fabri. Their structures were elucidated by extensive analysis of NMR data. The electronic circular dichroism was utilized to assign the absolute configuration of 1. Compounds 1 and 2 showed significant cytotoxic activities against ZR-75-30 tumor cell with IC₅₀ values of 6.26 and 1.63 μg/mL, respectively.     

Arylnaphthalide lignans from Saussurea medusa and their anti-inflammatory activities

Five new arylnaphthalide lignans (1 ? 4a/4b), together with five known analogues (5–9), were isolated from whole plants of Saussurea medusa. Compound 4 was characterized as an aryltetralin lignan with an unusual C-7′-C-9 oxygen bridge group, and a chiral HPLC analysis was carried out to afford one pair of enantiomers (4a/4b). Structures of the new compounds were elucidated by extensive spectroscopic and electronic circular dichroism (ECD) calculations. All compounds were firstly isolated from S. medusa, and compounds 1–5, 7 and 8 had never been obtained from the genus Saussurea previously. Furthermore, this is the first report of arylnaphthalide lignans isolated from S. medusa. anti-inflammatory activities of the compounds were evaluated by determining their inhibitory activities on the production of NO by LPS-stimulated RAW 264.7 cells. Compounds (?)-4a and 5 exerted the significant inhibition activities with IC₅₀ values of 13.4 ± 1.5 and 15.7 ± 1.1 μM, respectively, which even exceeded the positive control quercetin (IC₅₀ = 15.9 ± 1.2 μM). Compounds 2, (+)-4b, 6 and 9 exhibited moderate inhibitory activities with IC₅₀ values ranging from 19.7 ± 1.9 to 47.4 ± 3.1 μM. Further analysis by molecular docking showed that almost all the active compounds could interact with the amino acid residues of iNOS proteins, which also supported their anti-inflammatory activities.     

Neolignan and phenylpropanoid compounds from the fruits of Illicium simonsii Maxim

One new sesqui-neolignan compound, namely, sesqui-illisimonan A (1), one new neolignan, illisimonan A (2), and one new phenylpropanoid compound, illisimoid A (3) were isolated from the fruits of Illicium simonsii Maxim. The structures and absolute configurations of these compounds were determined by extensive spectroscopic, including NMR, circular dichroism and calculated electronic circular dichroism methods. The antioxidant activities of compounds 1–3 were also evaluated. Vitamin E was selected as the positive control (IC₅₀ = 49.73 ± 0.88 μM). Compounds 1 and 2 exhibited in vitro antioxidant activity with an IC₅₀ value of 55.76 ± 1.30 and 59.36 ± 0.50 μM, respectively. However, the compound 3 didn’t show obvious antioxidant activity.     

Eight new polyketide metabolites from the fungus Pestalotiopsis vaccinii endogenous with the mangrove plant Kandelia candel (L.) Druce

Seven new prenylated phenols, vaccinols A–G (1–7), and one new naphthalene derivative, vaccinal A (8), together with five known phenol derivatives (9–13) were isolated from Pestalotiopsis vaccinii (cgmcc3.9199) endogenous with the mangrove plant Kandelia candel (L.) Druce (Rhizophoraceae). The new structures were established on the basis of spectroscopic analysis, optical rotation, CD spectra, quantum ECD calculations. Furthermore, the absolute configuration of compound 1 was unambiguously elucidated by single-crystal X-ray diffraction analysis using the Flack parameter. Most new compounds were tested for their antiviral (EV71), cytotoxic, antituberculosis, and anti-inflammatory effects. Among them, compound 8 exhibited in vitro anti-enterovirus 71 (EV71) with IC₅₀ value of 19.2 μM. In addition, 8 showed potent COX-2 inhibitory activity with IC₅₀ value of 1.8 μM.     

Cytotoxic gephyromycins from the Streptomyces sp. SS13I

Two new gephyromycins (1–2), belonging to angucyclinones, were identified from Streptomyces sp. SS13I. Their structures were elucidated by analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and the structure of 1 was further elucidated by X-ray diffraction data. The absolute configurations of compounds 1–2 were evidenced by ECD calculations. To our best knowledge, Compounds 1–2 were the second reported gephyromycin-type angucyclinones. Compound 2 exhibited significant cytotoxicity against PC3 cell lines with IC₅₀ values of 1.38 ± 0.47 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 cytotoxic dimeric furanoheliangolide from Piptocoma rufescens

A new sesquiterpene lactone, rufescenolide C (1), the first furanoheliangolide dimer, was isolated from the leaves of Piptocoma rufescens, collected in the Dominican Republic. Its structure was determined by interpretation of its spectroscopic data, with the absolute configuration being established by analysis of the CD spectrum. A plausible biogenesis of this dimer is proposed. This compound showed potent cytotoxicity with an IC₅₀ value of 150 nM, when tested against HT-29 human colon cancer cells.     

Synthesis, α-glucosidase inhibition and molecular docking studies of natural product 2-(2-phenyethyl)chromone analogues

A series of natural product (2-phenyethyl)chromone analogues (3–34) were designed, synthesized, and screened for their α-glucosidase inhibitory activity. The results indicated that some of the synthesized derivatives displayed inhibitory activities against α-glucosidase with IC₅₀ values ranging from 11.72 ± 0.08 to 85.58 ± 2.30 μM when compared to the standard drug acarbose (IC₅₀ = 832.22 ± 2.00 μM). Among them, compound 4 with a hydroxyl group at the 7-position of chromone and a chloro group at the 4-position of the benzene ring, displayed the most significant inhibitory activity with the IC₅₀ value of 11.72 ± 0.08 μM. The inhibitory mechanism of compound 4 against α-glucosidase was studied by enzyme kinetic, circular dichroism spectra, fluorescence quenching, and molecular docking. Sucrose loading test in vivo further demonstrated that it could decrease blood glucose levels after sucrose administration in normal Kunming mice. In vitro cytotoxicity showed that 4 exhibited low cytotoxicity against normal human cell lines. The ADME study suggested that all compounds are likely to be orally active as they obeyed Lipinski’s rule of five. In summary, our studies showed that these derivatives are a new class of α-glucosidase inhibitors.     

Neuroprotective constituents from the fruits of Maclura tricuspidata

Cudraisoflavone L ? T (1–11), cudradihydrochalcone A (12), and cudrabibenzyl A (13), together with 41 known constituents, were isolated from the fruits of Maclura tricuspidata (formerly known as Cudrania tricuspidata). Their structures were determined by spectroscopic and chemical methods including electronic circular dichroism. All isolated compounds were evaluated for their neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced cell death in human neuroblastoma SH-SY5Y cells, of these six compounds exhibited activities with EC₅₀ values of 4.5–18.6 μM. Furthermore, the neuroprotective effects against oxygen glucose deprivation (OGD)-induced cell death of all isolated constituents, together with 37 previously reported isoflavones were evaluated. Four compounds showed neuroprotective activities with EC₅₀ values of 3.5–11.9 μM.