Benzophenones from Guignardia sp. IFB‐E028, an Endophyte on Hopea hainanensis

The first natural S‐containing benzophenone dimer, named guignasulfide ( 3 ), was isolated from the culture of Guignardia sp. IFB‐E028, an endophytic fungus residing in healthy leaves of Hopea hainanensis. Its structure was determined through correlative analyses of its MS, 1D‐ and 2D‐NMR spectroscopic data. Two other known benzophenone derivatives, monomethylsulochrin and rhizoctonic acid ( 1 and 2 , resp.) were also isolated. Guignasulfide ( 3 ) was more active against the human liver cancer cell line HepG2 (IC₅₀ value: 5.2±0.4 μM ) than metabolites 1 and 2 (IC₅₀ values: 63.5±0.6 and 60.2±0.5 μM ); compounds 1 – 3 showed also moderately inhibitory effects on the human bacterial pathogen Helicobacter pylori with MIC values of 28.9±0.1, 60.2±0.4, and 42.9±0.5 μM , respectively.     

A New Benzoylphloroglucinol Derivative with an Adamantyl Skeleton and Other Constituents from Garcinia multiflora: Effects on Neutrophil Pro‐Inflammatory Responses

A novel benzoylphloroglucinol derivative, garcimultiflorone D ( 1 ), with an unusual adamantyl‐caged skeleton was isolated from the fruits of Garcinia multiflora, together with four known compounds. The structure of 1 was determined through extensive 1D/2D‐NMR and mass‐spectrometric analyses. Garcimultiflorone D ( 1 ) exhibited inhibitory activities with IC₅₀ values of 7.21±1.07 and 6.01±0.37 μg/ml against fMLP/CB‐induced superoxide anion generation and elastase release, respectively.     

α‐Glucosidase Inhibitory Xanthones from the Roots of Garcinia fusca

Two new compounds, fuscaxanthones J ( 1 ) and K ( 2 ), together with eight known xanthones ( 3 – 10 ) were isolated from an ethyl acetate extract of the roots of Garcinia fusca. Their structures were determined using spectroscopic methods, mainly 1D‐ and 2D‐NMR. α‐Glucosidase inhibitory activity of the isolated compounds was evaluated and fuscaxanthone J ( 1 ) showed the most significant effect with an IC₅₀ value of 8.3 ± 1.8 μm (compared with acarbose, IC₅₀ = 214.5 ± 2.3 μm ).     

Inhibitory Effects of Constituents of an Endophytic Fungus Hypoxylon investiens on Nitric Oxide and Interleukin‐6 Production in RAW264.7 Macrophages

Three new compounds, hypoxyloamide ( 1 ), 8‐methoxynaphthalene‐1,7‐diol ( 2 ), and hypoxylonol ( 3 ), together with seven compounds isolated from nature for the first time, investiamide ( 4 ), hypoxypropanamide ( 5 ), hypoxylonol A ( 6 ), investienol ( 7 ), 2‐heptylfuran ( 8 ), (3S)‐5‐methyl‐8‐O‐methylmellein ( 9 ), (4R)‐O‐methylsclerone ( 10 ), along with 19 known compounds, 11 – 29 , were isolated from the culture broth of Hypoxylon investiens BCRC 10F0115, a fungal endophyte residing in the stems of an endemic Formosan plant Litsea akoensis var. chitouchiaoensis. The structures of the new compounds were established by spectroscopic methods, including UV, IR, HR‐ESI‐MS, and extensive 1D‐ and 2D‐NMR techniques. Of these isolates, 2 , 8‐methoxynaphthalen‐1‐ol ( 15 ), and 1,8‐dimethoxynaphthalene ( 16 ) showed nitric oxide (NO) inhibitory activity with IC₅₀ values of 11.8±0.9, 17.8±1.1, and 13.3±0.5 μM , respectively, stronger than the positive control quercetin (IC₅₀ 36.8±1.3 μM ). Compounds 2, 15 , and 16 also showed interleukin‐6 (IL‐6) inhibitory activity with IC₅₀ values of 9.2±1.7, 18.0±0.6, and 2.0±0.1 μM , stronger than the positive control quercetin (IC₅₀ 31.3±1.6 μM ). To the best of our knowledge, this is the first report on guaiane sesquiterpene metabolites, 3, 6 , and 7 , from the genus Hypoxylon.     

New cytotoxic metabolites from a deep-sea-derived fungus, Phialocephala sp., strain FL30r

Two new sorbicillinoids, 1 and 2 , together with a novel benzofuranone derivative named phialofurone ( 3 ), were isolated from a deep‐sea sediment‐derived fungus, Phialocephala sp. Their structures were established on the basis of spectroscopic data. All compounds displayed cytotoxic effects against P388 (IC₅₀ values of 11.5±1.4, 0.1±0.1, and 0.2±0.01 μM , resp.) and K562 (IC₅₀ values of 22.9±0.8, 4.8±0.3 and 22.4±0.9 μM , resp.) cell lines.     

New Cytotoxic Alkylated Chalcones from Fatoua villosa

Three new alkylated chalcones, villosins A – C ( 1  –  3 ), five known analogues, together with ten known coumarins, were isolated from Fatoua villosa. The structures of the new compounds were elucidated by extensive spectroscopic analysis, including 1D‐, 2D‐NMR, and MS data. Compounds 1  –  3 showed cytotoxicity against five kinds of human tumor cell lines (NB4, A549, SHSY5Y, PC3, and MCF7) with IC₅₀ values ranging from 1.4 ± 0.1 to 5.7 ± 0.3 μm .     

New Thymol Derivatives and Cytotoxic Constituents from the Root of Eupatorium cannabinum ssp. asiaticum

Two new thymol (=5‐methyl‐2‐(1‐methylethyl)phenol) derivatives, 8,10‐didehydro‐9‐(3‐methylbutanoyl)thymol 3‐O‐tiglate ( 1 ) and 9‐O‐angeloyl‐8‐methoxythymol 3‐O‐isobutyrate ( 2 ), were isolated from the root of Eupatorium cannabinum ssp. asiaticum, together with six known compounds, 3 – 8 . The structures of 1 and 2 were determined through extensive 1D/2D‐NMR and MS analyses. Among the isolates, 9‐acetoxy‐8,10‐epoxythymol 3‐O‐tiglate ( 3 ) was the most cytotoxic, with IC₅₀ values of 0.02±0.01, 1.02±0.07, and 1.36±0.12 μg/ml, respectively, against DLD‐1, CCRF‐CEM, and HL‐60 cell lines. In addition, 10‐acetoxy‐9‐O‐angeloyl‐8‐hydroxythymol ( 4 ) and eupatobenzofuran ( 6 ) exhibited cytotoxicities, with IC₅₀ values of 1.14±0.16 and 2.63±0.22, and 7.63±0.94 and 2.31±0.14 μg/ml, respectively, against DLD‐1 and CCRF‐CEM cell lines.     

Cytotoxic and Anti‐inflammatory Sesquiterpenes from Ainsliaea henryi

Three new sesquiterpenoids, 4α‐hydroxyeudesm‐11(13)‐en‐12‐yl 3‐methylbutanoate ( 1 ), diaspanolide E ( 2 ), and (13α)‐germacra‐1(10),4‐dien‐12,8α‐olid‐15‐oic acid ( 3 ), along with eight known sesquiterpenoids ( 4 – 11 ), were isolated from the aerial parts of Ainsliaea henryi. The chemical structures of compounds 1 – 3 were elucidated by spectroscopic analysis (1D‐, 2D‐NMR, MS and HR/MS). All isolates were evaluated for their inhibitory activities against nitric oxide (NO) production in lipopolysaccharide‐induced RAW264.7 macrophage cells. Compound 10 exhibited significantly inhibition against NO release with an IC₅₀ value of 6.54 ± 0.16 μm . Also, all isolated compounds were tested for cytotoxicity against three human tumor cell lines A549, MGC803, and HCT116, among which compound 5 significantly inhibited the proliferation of MGC803 cell lines with an IC₅₀ value of 2.2 ± 0.2 μm .     

A New Aromatic Amide from the Roots of Zanthoxylum tessmannii (Rutaceae)

Phytochemical investigation of the methanolic extract of the roots of Zanthoxylum tessmannii Zepernick and Timler (Rutaceae) led to the isolation and characterization of one new aromatic amide named tessmamide ( 1 ) along with twelve known compounds, N‐benzoyltyramine methyl ether ( 2 ), 7,8,9‐trimethoxycoumarin ( 3 ), 7,8‐dimethoxycoumarin ( 4 ), integrifoliodiol ( 5 ), robustin ( 6 ), skimmianine ( 7 ), lupeol ( 8 ), lupenone ( 9 ), a mixture of stigmasterol and β‐sitosterol, and a mixture of their glucosides. The structures of all compounds were determined by comprehensive spectroscopic analyses (1D‐ and 2D‐NMR, EI‐MS, and ESI‐MS) and comparison with known analogs. The determination of the radical scavenging activity using the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) assay gave moderate antioxidant values for the crude extracts of the roots of Zanthoxylum tessmannii (IC₅₀ 0.8 mg/mL), tessmamide ( 1 ; IC₅₀ 31.8 μm ), and 7,8,9‐trimethoxycoumarin ( 3 ; IC₅₀ 29.3 μm ), compared to the standard ascorbic acid (IC₅₀ 11.6 μm ).     

Bergamotane Sesquiterpenes with Alpha‐Glucosidase Inhibitory Activity from the Plant Pathogenic Fungus Penicillium expansum

Two new bergamotane sesquiterpene lactones, named expansolides C and D ( 1 and 2 ), together with two known compounds expansolides A and B ( 3 and 4 ), were isolated from the plant pathogenic fungus Penicillium expansum ACCC37275. The structures of the new compounds were established by detailed analyses of the spectroscopic data, especially 1D‐, 2D‐NMR, and HR‐ESI‐MS. In an in vitro bioassay, the epimeric mixture of expansolides C and D ( 1 and 2 ) (in a ratio of 2:1 at the temprature of the bioassay) exhibited more potent α‐glucosidase inhibitory activity (IC₅₀ =0.50 ± 0.02 mm ) as compared with the positive control acarbose (IC₅₀ = 1.90 ± 0.05 mm ). To the best of our knowledge, it was the first report on the α‐glucosidase inhibitory activity of bergamotane sesquiterpenes.     

Sesquiterpene Lactones with COX‐2 Inhibition Activity from Artemisia lavandulaefolia

Two new sesquiterpene lactones, artelavanolides A ( 1 ) and B ( 2 ), and four known sesquiterpene lactones ( 3 – 6 ) were isolated from the leaves of Artemisia lavandulaefolia. Their structures were elucidated based on the analysis of spectroscopic data (1D, 2D‐NMR and HR‐ESI‐MS). The absolute configuration of 1 was determined by the analysis of single‐crystal X‐ray diffraction data. Artelavanolide A ( 1 ) is a rare sesquiterpene lactone possessing an unusual skeleton with the linkage of Me(14)–C(1) that is probably formed through a rearrangement of the guaiane‐type sesquiterpenoids. Artelavanolide B ( 2 ) is a new highly unsaturated guaianolide. Compounds 1 – 6 were tested for activities on the inhibition of COX‐2 enzyme in vitro. All of compounds exhibited inhibitory activity against COX‐2 with IC₅₀ values ranging from 43.29 to 287.07 μm compared with the positive control, celecoxib (IC₅₀ = 18.10 μm ). Among them, 3 showed the best COX‐2 inhibitory activity with an IC₅₀ value of 43.29 μm .     

Caryophyllene Sesquiterpenes from Pulicaria vulgaris Gaertn.: Isolation,Structure Determination,Bioactivity and Structure−Activity Relationship

A new caryophyllene, named pulicaryenne A ( 1 ), along with four other known caryophyllene derivatives ( 2 , 3 , 4 and 5 ) were isolated from the ethyl acetate extract of aerial parts of Pulicaria vulgaris Gaertn . (Asteraceae). All compounds were isolated for the first time from this species. Compound 2 was identified as a new epimer of a known caryophyllene derivative isolated previously from P. dysenterica. Their structures were established by spectroscopic means including NMR analysis (1D‐ and 2D‐NMR) and ESI‐TOF‐MS. All compounds were evaluated for their anticholinesterase, antityrosinase and cytotoxic activities against two human cell lines (A549 and HeLa). Results showed that compound 5 exhibited the highest cytotoxic effect against A549 and anticholinesterase activity with IC₅₀ values of 8.50±0.75 and 6.45±0.09 μg/mL, respectively. Furthermore, compound 5 showed also an interesting antityrosinase activity with percent inhibition value of 79.0±2.5 % at 50 μg/mL. The bioactivity and drug likeness scores of the isolated compounds 1–5 were calculated using Molinspiration software and discussed. These results may suggest that the five caryophyllene derivatives endowed with good biological properties, which could be used as bioactive alternatives in pharmaceutical preparations.     

Synthesis and Characterization of Novel Thiazolo[3,2‐a]pyrimidine Derivatives and Evaluation of Antioxidant and Cytotoxic Activities

A series of novel thiazolo[3,2‐a]pyrimidines were synthesized and characterized by FT‐IR, ¹H, ¹³C‐NMR and mass techniques. Their antioxidant activities were investigated by 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging assay and the results showed that all the synthesized compounds exhibit good antioxidant activity. In addition, it was found that any substituent on the aromatic ring of the products plays an important role in their antioxidant activity. In vitro cytotoxicity of compounds 4a – 4j was investigated using MTT cell viability assay. Among these compounds, 6‐ethyl 2,3‐dimethyl 5‐(4‐chlorophenyl)‐7‐methyl‐2,3‐dihydro‐5H‐[1,3]thiazolo[3,2‐a]pyrimidine‐2,3,6‐tricarboxylate ( 4e ) bearing a chlorine substituent displayed the highest cytotoxic effect (IC₅₀=6.26±0.6 μm ) in comparison with doxorubicin (IC₅₀=0.68±0.1 μm ) as a standard after 72 h. Therefore, it is assumed that these compounds could be used as effective antioxidant and cytotoxic agents.     

Chemical Constituents of the Vietnamese Marine Sponge Gelliodes sp. and Their Cytotoxic Activities

A new decenoic acid derivative, gelliodesinic acid, and a naturally new alkaloid, together with three known furanoterpenoids and two known indole alkaloids, were isolated from the MeOH extract of the marine sponge Gelliodes sp. collected in Vietnam. The chemical structures of the isolated compounds were determined by analyses of 1D‐ and 2D‐NMR and MS data and by comparisons of the data with those reported in the literature. The cytotoxicity assay against HeLa, MCF‐7, and A549 cancer cell lines revealed that the three known furanoterpenes exhibited cytotoxic activities with IC₅₀ values ranging from 23.6 to 75.5 μM against the three cell lines, and that 1H‐indole‐3‐carboxylic acid showed cytotoxicity with an IC₅₀ value of 89.2 μM against A549 cancer cell lines.     

Lavandulyl Flavanones from the Stems of Hypericum calycinum L.

One novel lavandulyl flavanone (=2,3‐dihydro‐2‐phenyl‐4H‐1‐benzopyran‐4‐one) with an unusual 5,2′,4′,6′‐tetrahydroxy substitution, calycinigin A ( 1 ), was isolated from the stems of Hypericum calycinum L. (Hypericaceae). The structure was elucidated on the basis of 1D‐ and 2D‐NMR analysis, as well as mass spectrometry (LR‐EI‐ and HR‐EI‐MS) and circular dichroism. Three known lavandulyl flavanones with 5,7,2′,4′,6′‐pentahydroxy substitution, i.e., 2 – 4 , were also isolated. Chemosystematically, this is the first report on the occurrence of prenylated flavanones in the family Hypericaceae. Reduction of cell viability by all compounds was evaluated in a MTT (=3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) assay using HeLa cells. Compound 1 showed moderate activity with an IC₅₀ value of 9.7±1.8 μM , whereas compounds 2 – 4 were less active exhibiting IC₅₀ values of 11.6±0.9, 19.3±1.5, and 40.7±2.4 μM , respectively. The antioxidant activity was evaluated by an ORAC (Oxygen Radical Absorbance Capacity) assay, and calycinigin A ( 1 ) was again the most active compound with a Trolox equivalent of 2.3±0.2. None of the compounds was able to reduce the TNF‐α induced ICAM‐1 expression in vitro using human microvascular endothelial cells (HMEC‐1).     

Sesquiterpenoid Compounds from Curcuma kwangsiensis

Two previously undescribed guaiane‐type sesquiterpenes ( 1 and 2 ), a pair of new salvialane‐type sesquiterpenes ( 3a and 3b ), together with 11 known compounds were isolated and purified from the rhizomes of Curcuma kwangsiensis. Their structures were elucidated by the extensive spectroscopic data (1D‐ and 2D‐NMR) analysis. All the isolated compounds were assessed for their anti‐neuroinflammatory activity by inhibiting the nitric oxide (NO) production in lipopolysaccharide (LPS)‐activated murine BV‐2 microglial cells in vitro assay, and the isolates 3 and 11 showed anti‐neuroinflammatory activity with IC₅₀ values of 1.85 and 20.05 μm , respectively.     

Biological Evaluation of Secondary Metabolites from the Root of Machilus obovatifolia

Bioassay‐guided fractionation of the root of Machilus obovatifolia led to the isolation of four new lignans, epihenricine B ( 1 ), threo‐(7′R,8′R) and threo‐(7′S,8′S)‐methylmachilusol D ( 2 and 3 ), and isofragransol A ( 4 ), along with 23 known compounds. The compounds were obtained as isomeric mixtures (i.e., 2 / 3 and 4 / 20 , resp.). The structures were elucidated by spectral analyses. Among the isolates, 1 , licarin A ( 12 ), guaiacin ( 14 ), (±)‐syringaresinol ( 21 ), and (?)‐epicatechin ( 23 ) showed ABTS (=2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) cation radical‐scavenging activity, with SC₅₀ values of 11.7±0.5, 12.3±1.1, 11.0±0.1, 10.6±0.3, and 9.5±0.2 μM in 20 min, respectively. In addition, kachirachirol B ( 17 ) showed cytotoxicity against the NCI‐H460 cell line with an IC₅₀ value of 3.1 μg/ml.     

An Unusual Tetrahydrofuran Lignan from the Roots of Zanthoxylum planispinum and the Potential Anti‐inflammatory Effects

An unusual tetrahydrofuran lignin, zanthplanispine ( 1 ), together with 14 known lignans ( 2 – 15 ) were isolated from the AcOEt‐soluble fraction from the MeOH extract of Z. planispinum roots. The structures of 1 was elucidated on the basis of 1D‐ and 2D‐NMR experiments as well as HR‐ESI‐MS analysis. The known compounds were identified by the comparison of their NMR data with previously reported in the literatures. Bioassay showed that compounds 1 – 4 could inhibit nitric oxide (NO) production in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. In particular, compound 1 showed significant inhibitory activity with an IC₅₀ value of 36.8 μm .     

Westalsan: A New Acetylcholine Esterase Inhibitor from the Endophytic Fungus Westerdykella nigra

A new cytochalasan alkaloid, westalsan ( 1 ), along with two known cytochalasan compounds, phomacin B ( 2 ) and 19-hydroxy-19,20-dihydrophomacin C ( 3 ), were isolated from the solid rice culture of Westerdykella nigra, a marine-derived endophytic fungus, isolated from the roots of mangrove Avicennia marina (Forssk.) Vierh. The structures of compounds 1 – 3 were established on the basis of extensive 1D and 2D NMR spectroscopic techniques in combination with HR-ESI-MS. The ability of the isolated compounds to inhibit acetylcholine esterase activity was evaluated. Compound 3 showed the highest acetylcholine esterase inhibitory activity (IC₅₀ 0.056±0.003 μM), followed by compound 1 (IC₅₀ 0.088±0.005 μM) and compound 2 (IC₅₀ 0.140±0.007 μM) compared to donepezil (IC₅₀ 0.035±0.002 μM). This was further confirmed by molecular docking experiment.     

Secolignans with antiangiogenic activities from Peperomia dindygulensis

Two new secolignans, peperomins G and H ( 1 and 2 , resp.), were isolated from the whole plant of Peperomia dindygulensis, together with five known secolignans, peperomin A ( 3 ), peperomin E ( 4 ), peperomin B ( 5 ), 2,3‐trans‐2‐methyl‐3‐{(3‐hydroxy‐4,5‐dimethoxyphenyl)[5‐methoxy‐3,4‐(methylenedioxy)phenyl]methyl}butyrolactone ( 6 ), 2,3‐cis‐2‐(hydroxymethyl)‐3‐{bis[5‐methoxy‐3,4‐(methylenedioxy)phenyl]methyl}butyrolactone ( 7 ). Their structures and configurations were elucidated by spectroscopic methods including 2D‐NMR techniques. Antiangiogenic effects of all compounds were evaluated using human umbilical vein endothelial cells (HUVEC) proliferation and tube‐formation tests, with compounds 4 and 5 being active in the bioassay. Compounds 4 and 5 induced obvious cell toxicity to HUVEC with IC₅₀ values of 1.64±0.19 and 8.44±0.4 μM , respectively. Compounds 4 and 5 also exhibited significant HUVEC tube formation‐inhibiting activity with IC₅₀ values of 3.13±0.09 and 6.24±0.12 μM , respectively.