Antifungal Monoterpene Derivatives from the Plant Endophytic Fungus Pestalotiopsis foedan

A new monoterpene lactone, (1R,4R,5R,8S)‐8‐hydroxy‐4,8‐dimethyl‐2‐oxabicyclo[3.3.1]nonan‐3‐one ( 1 ), along with one related known compound, (2R)‐2‐[(1R)‐4‐methylcyclohex‐3‐en‐1‐yl]propanoic acid ( 2 ), were isolated from the liquid culture of the plant endophytic fungus Pestalotiopsis foedan obtained from the branch of Bruguiera sexangula. The structure and absolute configuration of 1 were determined on the basis of extensive analysis of NMR spectra combined with computational methods via calculation of the optical rotation (OR) and ¹³C‐NMR. Both compounds exhibited strong antifungal activities against Botrytis cinerea and Phytophthora nicotianae with MIC values of 3.1 and 6.3 μg/ml, respectively, which are comparable to those of the known antifungal drug ketoconazole. Compound 2 also showed modest antifungal activity against Candida albicans with a MIC value of 50 μg/ml.     

Chemical Constituents from the Flowers of Wild Gardenia jasminoides J.Ellis

Four new iridoids, 2′‐O‐(E)‐coumaroylshanzhiside ( 1 ), 6′‐O‐(E)‐coumaroylshanzhiside ( 2 ), 8α‐butylgardenoside B ( 3 ), 6α‐methoxygenipin ( 4 ), and one new phenylpropanoid glucoside, 5‐(3‐hydroxypropyl)‐2‐methoxyphenyl β‐d ‐glucopyranoside ( 5 ), together with sixteen known compounds, were isolated from the edible flowers of wild Gardenia jasminoides J.Ellis . Their chemical structures were characterized by extensive spectroscopic techniques, including 1D‐ and 2D‐NMR, HR‐ESI‐MS, and CD experiments. The absolute configurations of the new isolates’ sugar moiety were assigned by HPLC analysis of the acid hydrolysates. Furthermore, the antioxidant activities of those isolates were preliminarily evaluated by DPPH scavenging experiment. And comparison of ¹H‐NMR spectra for the EtOH extract of G. jasminoides J.Ellis , gardenoside B and geniposide revealed that the flowers of this plant have a considerable content of gardenoside B instead of geniposide in the fruits, indicating different activities and applications in people's daily life.     

Iridoids from Pedicularis verticillata and Their Anti‐Complementary Activity

Three new iridoids named as pediverticilatasin A – C ( 1 – 3 , resp.), together with five known iridoids ( 4 – 8 , resp.) were isolated from the whole plants of Pedicularis verticillata. The structures of three new compounds were identified as (1S,7R)‐1‐ethoxy‐1,5,6,7‐tetrahydro‐7‐hydroxy‐7‐methylcyclopenta[c]pyran‐4(3H)‐one ( 1 ), (1S,4aS,7R,7aS)‐1‐ethoxy‐1,4a,5,6,7,7a‐hexahydro‐7‐hydroxy‐7‐methylcyclopenta[c]pyran‐4‐carboxylic acid ( 2 ), (1S,4aS,7R,7aS)‐1‐ethoxy‐1,4a,5,6,7,7a‐hexahydro‐7‐hydroxy‐7‐methylcyclopenta[c]pyran‐4‐carbaldehyde ( 3 ). Their structures were elucidated on the basis of spectroscopic methods and compared with the NMR spectra data in the literature. All compounds were evaluated for their anti‐complementary activity on the classical pathway of the complement system in vitro. Among which, compounds 1 , 3 , and 6 exhibited anti‐complementary effects with CH₅₀ values ranging from 0.43 to 1.72 mm , which are plausible candidates for developing potent anti‐complementary agents.     

Microsphaerol and Seimatorone: Two New Compounds Isolated from the Endophytic Fungi,Microsphaeropsis sp. and Seimatosporium sp.

A new polychlorinated triphenyl diether named microsphaerol ( 1 ), has been isolated from the endophtic fungus Microsphaeropsis sp. An intensive phytochemical investigation of the endophytic fungus Seimatosporium sp., led to the isolation of a new naphthalene derivative named seimatorone ( 2 ) and eight known compounds, i.e., 1‐(2,6‐dihydroxyphenyl)‐3‐hydroxybutan‐1‐one ( 3 ), 1‐(2,6‐dihydroxyphenyl)butan‐1‐one ( 4 ), 1‐(2‐hydroxy‐6‐methoxyphenyl)butan‐1‐one ( 5 ), 5‐hydroxy‐2‐methyl‐4H‐chromen‐4‐one ( 6 ), 2,3‐dihydro‐5‐hydroxy‐2‐methyl‐4H‐chromen‐4‐one ( 7 ), 8‐methoxynaphthalen‐1‐ol ( 8 ), nodulisporins A and B ( 9 and 10 , resp.), and daldinol ( 11 ). The structures of 1 and 2 were elucidated by detailed spectroscopic analysis including ¹H‐ and ¹³C‐NMR, COSY, HMQC, HMBC, and HR‐EI‐MS, while the structures of the known compounds were deduced from comparison of their spectral data with those in the literature. Preliminary studies revealed that microsphaerol ( 1 ) showed good antibacterial activities against B. Megaterium and E. coli, and good antilagal and antifungal activities against C. fusca, M. violaceum, respectively. On the other hand, seimatorone ( 2 ) exhibited moderate antibacterial, antialgal, and antifungal activities.     

Lasiolactols A and B Produced by the Grapevine Fungal Pathogen Lasiodiplodia mediterranea

A strain of Lasiodiplodia mediterranea, a fungus associated with grapevine decline in Sicily, produced several metabolites in liquid medium. Two new dimeric γ‐lactols, lasiolactols A and B ( 1 and 2 ), were characterized as (2S*,3S*,4R*,5R*,2′S*,3′S*,4′R*,5′R*)‐ and (2R*,3S*,4R*,5R*,2′R*,3′S*,4′R*,5′R*)‐(5‐(4‐hydroxymethyl‐3,5‐dimethyl‐tetrahydro‐furan‐2‐yloxy)‐2,4‐dimethyl‐tetrahydro‐furan‐3‐yl]‐methanols by IR, 1D‐ and 2D‐NMR, and HR‐ESI‐MS. Other four metabolites were identified as botryosphaeriodiplodin, (5R)‐5‐hydroxylasiodiplodin, (–)‐(1R,2R)‐jasmonic acid, and (–)‐(3S,4R,5R)‐4‐hydroxymethyl‐3,5‐dimethyldihydro‐2‐furanone ( 3  –  6 , resp.). The absolute configuration (R) at hydroxylated secondary C‐atom C(7) was also established for compound 3 . The compounds 1  –  3 , 5, and 6 , tested for their phytotoxic activities to grapevine cv. Inzolia leaves at different concentrations (0.125, 0.25, 0.5, and 1 mg/ml) were phytotoxic and compound 5 showed the highest toxicity. All metabolites did not show in vitro antifungal activity against four plant pathogens.     

New Lignans from the Flower of Forsythia koreana and Their Suppression Effect on VCAM‐1 Expression in MOVAS Cells

Six lignans including two new lignans were obtained as the principal components of the Forsythia koreana flowers via silica gel (SiO₂), octadecyl SiO₂ (ODS) as well as Sephadex LH‐20 column chromatography. In addition to two new lignans, named koreanaside A ((7R,8S,7′R,8′S)‐7,7′‐diepoxy‐5′‐hydroxy‐3,3′‐dimethoxylignan 4‐O‐β‐d ‐glucopyranoside) and koreanaside B ((7R,8S,7′S,8′R)‐7,9′‐epoxy‐9,5′,7′‐trihydroxy‐3,3′‐dimethoxylignan 4‐O‐β‐d ‐glucopyranoside), four known lignans were identified to be (+)‐phylligenin, (?)‐epipinoresinol, pinoresinol, and tinosposide A. The structures and absolute configurations of koreanasides A and B were established by means of analysis of spectroscopic data (NMR, IR, FAB‐MS, and CD), whereas the structures of known lignans were identified by comparison their NMR and MS values with those in the reported literature. Their chemical structures including configuration were established by means of analysis of spectroscopic data (NMR, IR, FAB‐MS, and CD) but also comparison of their NMR and MS values with those in the reported literature. This is the first article for isolation of six lignans of F. koreana flowers. Koreanasides A and B showed high radical scavenging activity with oxygen radical absorbance capacity (ORAC) values of 0.97 ± 0.01 and 1.02 ± 0.01, respectively. Koreanaside A also prohibited expressing VCAM‐1 in MOVAS cells with 80.5% at 25 mg/mL.     

Sesquiterpene Lactones from Centaurea zuccariniana and Their Antimicrobial Activity

Twenty‐nine compounds were isolated from the aerial parts of the Greek plant C. zuccariniana DC. The structures of the isolated compounds were established by means of NMR‐ (¹H,¹H‐COSY, ¹H,¹³C‐HSQC, HMBC, NOESY, and ROESY) and mass‐spectral analyses. These compounds comprise 13 sesquiterpene lactones, 14 flavonoids, two lignans, and one simple lactone. Among the isolated sesquiterpene lactones, three are new, namely one heliangolide, (1E,4Z)‐15‐hydroxy‐8α‐O‐(4′‐acetoxy‐3′‐hydroxy‐2′‐methylidenebutanoyl)‐6βH,7αH‐germacra‐1,4,11(13)‐trien‐6,12‐olide; and two eudesmanolides, 8α‐(4′,5′‐diacetoxyangeloyl)sonchucarpolide and one unusual eudesmanolide with an oxygenated bridge linking C(1) and C(4), named zuccarinin. The main sesquiterpene lactones were malacitenolide, cnicin, and 4′‐O‐acetylcnicin. These results are in agreement with those obtained from the previously studied Greek Centaurea sp. belonging to the section Acrolophus (Cass .) DC.; this finding could be of chemotaxonomic significance for the genus Centaurea. The in vitro antimicrobial activities of the isolated new sesquiterpene lactones were against eight bacteria and eight fungal species. A 96‐well microbioassay procedure for fast and easy evaluation of antibacterial and antifungal activities was applied to compare these compounds with commercial antibiotic and fungicide standards, and with previously isolated analogous sesquiterpene lactones tested by the same bioassay. All of the compounds tested showed moderate antibacterial, but significant antifungal activities; the present results corroborate with previous data, indicating that these types of compounds exhibit low or moderate antibacterial, but potent antifungal activities. The unusual eudesmanolide zuccarinin proved to be the most potent among the present tested sesquiterpene lactones, as well as among all previously tested eudesmanolides isolated from Greek Centaurea sp.     

Novel Flavones from the Root of Phytolacca acinosa Roxb.

Two new flavones, 6,7‐methylenedioxy‐4‐hydroxypeltogynan‐7′‐one ( 1 ), cochliophilin B ( 2 ), as well as two known ones, cochliophilin A ( 3 ) and 6‐methoxy‐7‐hydroxy flavone ( 4 ), were isolated from the ethanol extract of the root of Phytolacca acinosa Roxb . Compound 1 is a flavanol framework with one δ‐lactone unit, which is rather rare in nature. The structures of the new compounds were determined on the basis of extensive spectroscopic (IR, MS, 1D‐ and 2D‐NMR) analyses, the absolute configuration of 1 was established by comparing experimental and calculated electronic circular dichroism spectra. The structures of known compounds were fixed by comparison with literatures data. Compounds 2 and 4 showed modest inhibitory activities against BEL‐7402 cell line, with IC₅₀ values of 28.22 and 39.16 μmol/L, respectively.     

New Isoprenylated 2‐Arylbenzofurans and Pancreatic Lipase Inhibitory Constituents from Artocarpus nitidus

Two new isoprenylated 2‐arylbenzofurans, artonitidin A (=(2′R)‐2′,3′‐dihydro‐2′‐(1‐hydroxy‐1‐methylethyl)‐5′,7‐bis(3‐methylbut‐2‐en‐1‐yl)‐2,4′‐bi‐1‐benzofuran‐6,6′‐diol; 1 ) and artonitidin B (=5‐[6‐hydroxy‐7‐(3‐methylbut‐2‐en‐1‐yl)‐1‐benzofuran‐2‐yl]‐4‐(3‐methylbut‐2‐en‐1‐yl)benzene‐1,3‐diol; 2 ), together with 14 known compounds, 3 – 16 , were isolated from the stems of Artocarpus nitidus Trec. The structures were elucidated by spectroscopic methods. Norartocarpin ( 3 ), cudraflavone C ( 5 ), brosimone I ( 8 ), artotonkin ( 11 ), albanin A ( 13 ), and artopetelin M ( 14 ) showed inhibitory effects on pancreatic lipase with IC₅₀ values ranging from 1.8±0.1 to 63.8±3.6 μM .     

Antimicrobial Compounds from Drypetes staudtii

Antimicrobial‐directed phytochemical investigation of the MeOH extract of Drypetes staudtii afforded two new compounds, 4,5‐(methylenedioxy)‐o‐coumaroylputrescine ( 1 ), 4,5‐(methylenedioxy)‐o‐coumaroyl‐4′‐N‐methylputrescine ( 2 ), along with seven known natural products 4α‐hydroxyeremophila‐1,9‐diene‐3,8‐dione ( 3 ), drypemolundein B ( 4 ), friedelan‐3β‐ol ( 5 ), erythrodiol ( 6 ), ursolic acid ( 7 ), p‐coumaric acid ( 8 ), and β‐sitosterol ( 9 ). Structures of compounds 1 – 9 were elucidated with the aid of extensive NMR and mass spectral studies. All of the isolates exhibited antibacterial activity against Gram‐positive and Gram‐negative bacteria with minimum inhibitory concentration (MIC) in the range of 8 – 128 μg/ml. Compounds 1 – 2 were also moderately active against Candida albicans with an MIC value of 32 μg/ml.     

A Cytotoxic Neolignan from Schisandra propinqua （Wall.） Baill.

In the course of our study of bioactive natural products from Schisandra plants, we isolated a neolignan from an EtOAc extract of the stems of Schisandra propinqua （Wall.） Baill. The structure of the new com- pound was determined to be 4, 4-di （4-hydroxy-3-methoxyphenly）-2, 3-dimethylbutanol （compound 1） on the basis of 1H- and 13C-NMR spectra and 2D NMR methods. Eight known compounds, compounds 2-9, were also isolated and identified, of which compounds 3, 4, 6 and 9 were isolated for the first time from this plant. In addition, compounds 1-4 were evaluated for cytotoxicity by an 3-（4,5-dimethyl-2 thiazoyl）-2,5-diphenyl-2H- tetrazolium bromide （MTT） assay. Compound 1 showed significant potential cytotoxic ability in the bioassay.     

A Novel Dimeric Coumarin Analog and Antimycobacterial Constituents from Fatoua pilosa

One novel dimeric coumarin analog, fatouapilosin ( 1 ), together with 18 known compounds, have been isolated from the whole plants of Fatoua pilosa. The structures of these isolates were elucidated by means of spectroscopic techniques (UV, IR, MS, ¹H‐ and ¹³C‐NMR, DEPT, COSY, NOESY, HSQC, HMBC, and MS analyses). Among the tested compounds 2 – 14 , scopoletin ( 3 ), isobavachalcone ( 12 ), and (E)‐1‐[2,4‐dihydroxy‐3‐(3‐methylbut‐2‐enyl)phenyl]‐3‐(2,2‐dimethyl‐8‐hydroxy‐2H‐benzopyran‐6‐yl)prop‐2‐en‐1‐one ( 14 ) exhibited the strongest antimycobacterial activities against Mycobacterium tuberculosis H₃₇Rv, with MIC values of 42, 18, and 30 μg/ml, respectively.     

Oplopane Sesquiterpenes from Ligularia knorringiana and Their Anti‐Complementary Activity

Three new oplopane sesquiterpenes, knorringianalarins D – F ( 1 – 3 , respectively), and five known analogues ( 4 – 8 , respectively), were isolated from the roots and rhizomes of Ligularia knorringiana. The structures of three new compounds were identified as 4‐acetoxy‐11α,12‐epoxy‐2β‐hydroxy‐3β‐(2‐methylbutyryloxy)‐9α‐(4‐methylsenecioyloxy)oplop‐10(14)‐ene ( 1 ), 3β,4‐diacetoxy‐9α‐(4‐acetoxy‐4‐methylsenecioyloxy)‐11α,12‐epoxy‐8α‐(2‐methylbutyryloxy)oplop‐10(14)‐ene ( 2 ), and (1R,5R,6R,7R,9R)‐5,9,11‐trihydroxy‐4,15‐dinoroplop‐10(14)‐en‐3‐one ( 3 ) based on spectroscopic methods including 1D‐ and 2D‐NMR, mass spectrometry, and CD spectroscopy techniques. All compounds were evaluated for their anti‐complementary activity on the classical pathway of the complement system in vitro. Among which, three oplopane sesquiterpenes ( 3 , 7 , and 8 ) exhibited better anti‐complementary effects with CH₅₀ values ranging from 0.33 to 0.89 mm , which are plausible candidates for developing potent anti‐complementary agents.     

13,14‐seco‐Withanolides from Physalis minima with Potential Anti‐inflammatory Activity

Four new 13,14‐seco‐withanolides, minisecolides A – D ( 1  –  4 ), together with three known analogues 5  –  7 , were isolated from the whole plants of Physalis minima. The structures of new compounds were determined on the basis of spectroscopic analysis, including ¹H‐, ¹³C‐NMR, 2D‐NMR (HMBC, HSQC, ROESY), and HR‐ESI‐MS. Evaluation of all isolates for their inhibitory effects on nitric oxide (NO) production was conducted on lipopolysaccaride‐activated RAW264.7 macrophages. Compounds 2 , 3 , 5 , and 6 showed inhibitory activities, especially for compound 5 with IC₅₀ value of 3.87 μm .     

Lignans from the Twigs of Euonymus alatus (Thunb.) Siebold and Their Biological Evaluation

A new sesquilignan, euonymolin A ( 1 ), and six known lignans, (?)‐de‐O‐methylmagnolin ( 2 ), (+)‐de‐O‐methylepimagnolin A ( 3 ), (+)‐syringaresinol ( 4 ), (+)‐pinoresinol ( 5 ), (+)‐medioresinol ( 6 ), and (+)‐lariciresinol 4′‐O‐β‐d ‐glucopyranoside ( 7 ), were isolated from the twigs of Euonymus alatus (Thunb .) Siebold (Celastraceae). The structures of the isolated compounds were elucidated based on spectroscopic analyses, including extensive 1D‐ and 2D‐NMR techniques, HR‐MS analysis and circular dichroism (CD) data, and the literature data. All of the isolated compounds were evaluated for antiproliferative activity against A549, SK‐OV‐3, SK‐MEL‐2, and HCT‐15 cell lines and inhibition of nitric oxide (NO) production in a lipopolysaccharide (LPS)‐activated BV2 cell line. All compounds showed cytotoxicity against the SK‐MEL‐2 cell line with IC₅₀ values of 23.24 – 48.14 μm and inhibited NO production in LPS‐activated BV‐2 cells with IC₅₀ values of 6.75 – 23.53 μm .     

Phialomyces macrosporus: Chemical Constituents,Antimicrobial Activity and Complete NMR Assignments for the 7,7′‐Biphyscion

Five known secondary metabolites, chrysophanol ( 1 ), 7,7′‐biphyscion ( 2 ), secalonic acid D ( 3 ), mannitol ( 4 ) and trehalose ( 5 ) were isolated for the first time from the extracts of the fungus Phialomyces macrosporus. Their structures were elucidated by NMR methods (1D and 2D NMR analysis), optical activity and ESI‐MS. Complete ¹H and ¹³C assignments were performed for compound 2 . The antimicrobial activity was evaluated by serial microdilution assay for compounds 2 and 3 and results showed that compound 3 exhibited a significant growth inhibition at concentrations of 15.6 mg/ml (S. aureus and S. choleraesius) and 0.97 mg/mL (B. subtilis), comparable to the positive control.     

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 .     

Chemical Components from Phaeanthus vietnamensis and Their Inhibitory NO Production in BV2 Cells

Phaeanthus vietnamensis Bân is a well‐known medicinal plant which has been used for the treatment of various inflammatory diseases in traditional medicine. Using various chromatographic methods, three new compounds, (7S,8R,8′R)‐9,9′‐epoxy‐3,5,3′,5′‐tetramethoxylignan‐4,4′,7‐triol ( 1 ), 8α‐hydroxyoplop‐11(12)‐en‐14‐one ( 5 ), and (1R,2S,4S)‐4‐acetyl‐2‐[(E)‐(cinnamoyloxy)]‐1‐methylcyclohexan‐1‐ol ( 12 ) along with twelve known compounds were isolated from the leaves of P. vietnamensis. Their chemical structures were elucidated by physical and chemical methods. All compounds were evaluated for the inhibitory activities of nitric oxide production in LPS‐stimulated BV2 cells. As the results, compound 6 showed the most potent inhibitory activity on LPS‐stimulated NO production in BV2 cells with the IC₅₀ values of 15.7 ± 1.2 μm . Compounds 2 , 7 , and 8 significantly inhibited inflammatory NO production with IC₅₀ values ranging from 22.6 to 25.3 μm .     

Resistance irrelevant CYP417A2v2 was found degrading insecticide in Laodelphax striatellus

Cytochrome P450 monooxygenases (CYP s) usually overexpressed in resistant strain were found involved in oxidative detoxification of insecticides. In this study, an investigation was conducted to confirm if resistance irrelevant CYP s which were not overexpressed in resistant strain before, were capable of degrading insecticides. Three resistance irrelevant CYP s viz. CYP 417A2v2, CYP 425A1v2, and CYP 4DJ 1 from CYP 4 family of Laodelphax striatellus were randomly selected for experiments. CYP 417A2v2 and CYP 425A1v2 were found expressed successfully in Sf9 cell line while CYP 4DJ 1 was not expressed successfully and out of two expressed CYP s, only CYP 417A2v2 showed its efficient catalytic activity. For catalytic activity, three traditional model probe substrates and five insecticides were assayed. For the probe substrates screened, p‐nitroanisole and ethoxycoumarin were preferentially metabolized by CYP 417A2v2 (specific activity 3.76 ± 1.22 and 1.63 ± 0.37 nmol min^?1 mg protein^?1, respectively) and they may be potential diagnostic probes for this enzyme. Among insecticides, only imidacloprid was efficiently degraded by CYP 417A2v2. Incubation of imidacloprid with CYP 417A2v2 of L. striatellus and subsequent HPLC , LC ‐MS , and MS /MS analysis revealed the formation of imidacloprid metabolites, that is, 4′ or 5′hydroxy‐imidacloprid by hydroxylation. This result implies the exemption of CYP s character that it is not always, all the CYP s degrading insecticides being selected and overexpressed in resistant strains and the degrading CYP s without mutations to upregulate could be candidates during insecticide resistance evolution. This characterization of individual insect CYP s in insecticide degradation can provide insight for better understand of insecticide resistance development.     

A Novel Monoterpene?Stilbene Adduct with a 4,4‐Dimethyl‐2,3‐diphenylchromane Skeleton from Artocarpus xanthocarpus

Artoxanthochromane ( 1 ), a Diels? Alder‐type conjugation product of 4‐isopropenylresorcinol and oxyresveratrol, was isolated from the heartwood of Artocarpus xanthocarpus and characterized. The structure of 1 was elucidated as 2‐(2,4‐dihydroxyphenyl)‐3‐(3,5‐dihydroxyphenyl)‐7‐hydroxy‐4,4‐dimethylchromane by 1D‐ and 2D‐NMR spectroscopy, and other spectral evidences. A plausible metabolic mechanism was proposed to illustrate the biosynthetic pathway of artoxanthochromane. This compound exhibited mild mushroom tyrosinase inhibitory, and weak free radical‐scavenging activities on ABTS^+. and superoxide anion (O ) free radicals.