Biphenyl‐Type Neolignan Derivatives from the Twigs of Magnolia denudata and Their Anti‐Inflammatory Activity

Two new biphenyl‐type neolignan derivatives, 2‐[2‐(hydroxymethyl)‐1‐benzofuran‐5‐yl]‐4‐(prop‐2‐en‐1‐yl)phenol ( 1 ) and 2′‐ethoxy‐5,5′‐di(prop‐2‐en‐1‐yl)biphenyl‐2‐ol ( 2 ), were isolated from the twigs of Magnolia denudata, together with six known compounds ( 3 – 8 ). The structures of 1 and 2 were determined through extensive 1D‐ and 2D‐NMR and mass‐spectrometric analyses. Magnolol ( 6 ) and honokiol ( 7 ) exhibited potent inhibition (IC₅₀ values=4.4±0.2 and 0.71±0.13 μg/ml, resp.) of O$\rm{{_{2}^{{^\cdot} -}}}$ generation by human nutrophils in response to N‐formyl‐L ‐methionyl‐L ‐leucyl‐L ‐phenylalanine/cytochalasin B (fMLP/CB). In addition, 2‐[2‐(hydroxymethyl)‐1‐benzofuran‐5‐yl]‐4‐(prop‐2‐en‐1‐yl)phenol ( 1 ), 2′‐ethoxy‐5,5′‐di(prop‐2‐en‐1‐yl)biphenyl‐2‐ol ( 2 ), magnolol ( 6 ), and vanillic acid ( 8 ) inhibited fMLP/CB‐induced elastase release with IC₅₀ values=6.4±1.5, 2.4±0.4, 1.5±0.2, and 4.8±0.5 μg/ml, respectively.     

New Alkaloids and α‐Glucosidase Inhibitory Flavonoids from Ficus hispida

Two new pyrrolidine alkaloids, ficushispimines A ( 1 ) and B ( 2 ), a new ω‐(dimethylamino)caprophenone alkaloid, ficushispimine C ( 3 ), and a new indolizidine alkaloid, ficushispidine ( 4 ), together with the known alkaloid 5 and 11 known isoprenylated flavonoids 6  –  16 , were isolated from the twigs of Ficus hispida. Their structures were elucidated by spectroscopic methods. Isoderrone ( 8 ), 3′‐(3‐methylbut‐2‐en‐1‐yl)biochanin A ( 11 ), myrsininone A ( 12 ), ficusin A ( 13 ), and 4′,5,7‐trihydroxy‐6‐[(1R*,6R*)‐3‐methyl‐6‐(1‐methylethenyl)cyclohex‐2‐en‐1‐yl]isoflavone ( 14 ) showed inhibitory effects on α‐glucosidase in vitro.     

Toxicity of Thiophenes from Echinops transiliensis (Asteraceae) against Aedes aegypti (Diptera: Culicidae) Larvae

Structure? activity relationships of nine thiophenes, 2,2′: 5′,2″‐terthiophene ( 1 ), 2‐chloro‐4‐[5‐(penta‐1,3‐diyn‐1‐yl)thiophen‐2‐yl]but‐3‐yn‐1‐yl acetate ( 2 ), 4‐(2,2′‐bithiophen‐5‐yl)but‐3‐yne‐1,2‐diyl diacetate ( 3 ), 4‐[5‐(penta‐1,3‐diyn‐1‐yl)thiophen‐2‐yl]but‐3‐yne‐1,2‐diyl diacetate ( 4 ), 4‐(2,2′‐bithiophen‐5‐yl)‐2‐hydroxybut‐3‐yn‐1‐yl acetate ( 5 ), 2‐hydroxy‐4‐[5‐(penta‐1,3‐diyn‐1‐yl)thiophen‐2‐yl]but‐3‐yn‐1‐yl acetate ( 6 ), 1‐hydroxy‐4‐[5‐(penta‐1,3‐diyn‐1‐yl)thiophen‐2‐yl]but‐3‐yn‐2‐yl acetate ( 7 ), 4‐(2,2′‐bithiophen‐5‐yl)but‐3‐yne‐1,2‐diol ( 8 ), and 4‐[5‐(penta‐1,3‐diyn‐1‐yl)thiophen‐2‐yl]but‐3‐yne‐1,2‐diol ( 9 ), isolated from the roots of Echinops transiliensis, were studied as larvicides against Aedes aegypti. Structural differences among compounds 3, 5 , and 8 consisted in differing AcO and OH groups attached to C(3″) and C(4″), and resulted in variations in efficacy. Terthiophene 1 showed the highest activity (LC₅₀, 0.16 μg/ml) among compounds 1 – 9 , followed by bithiophene compounds 3 (LC₅₀, 4.22 μg/ml), 5 (LC₅₀, 7.45 μg/ml), and 8 (LC₅₀, 9.89 μg/ml), and monothiophene compounds 9 (LC₅₀, 12.45 μg/ml), 2 (LC₅₀, 14.71 μg/ml), 4 (LC₅₀, 17.95 μg/ml), 6 (LC₅₀, 18.55 μg/ml), and 7 (LC₅₀, 19.97 μg/ml). These data indicated that A. aegypti larvicidal activities of thiophenes increase with increasing number of thiophene rings, and the most important active site in the structure of thiophenes could be the tetrahydro‐thiophene moiety. In bithiophenes, 3, 5 , and 8 , A. aegypti larvicidal activity increased with increasing number of AcO groups attached to C(3″) or C(4″), indicating that AcO groups may play an important role in the larvicidal activity.     

Bioactivity of natural O‐prenylated phenylpropenes from Illicium anisatum leaves and their derivatives against spider mites and fungal pathogens

A variety of volatile phenylpropenes, C₆‐C₃ compounds are widely distributed in the plant kingdom, whereas prenylated phenylpropenes are limited to a few plant species. In this study, we analysed the volatile profiles from Illicium anisatum leaves and identified two O‐prenylated phenylpropenes, 4‐allyl‐2‐methoxy‐1‐[(3‐methylbut‐2‐en‐1‐yl)oxy]benzene [O‐dimethylallyleugenol ( 9 )] and 5‐allyl‐1,3‐dimethoxy‐2‐(3‐methylbut‐2‐en‐1‐yl)oxy]benzene [O‐dimethylallyl‐6‐methoxyeugenol ( 11 )] as major constituents. The structure–activity relationship of a series of eugenol derivatives showed that specific phenylpropenes, including eugenol ( 1 ), isoeugenol ( 2 ) and 6‐methoxyeugenol ( 6 ), with a phenolic hydroxy group had antifungal activity for a fungal pathogen, whereas guaiacol, a simple phenolic compound, and allylbenzene had no such activity. The eugenol derivatives that exhibited antifungal activity, in turn, had no significant toxicant property for mite oviposition. Interestingly, O‐dimethylallyleugenol ( 9 ) in which the phenolic oxygen was masked with a dimethylallyl group exhibited a specific, potent oviposition deterrent activity for mites. The sharp contrast in structural requirements of phenylpropenes suggested distinct mechanisms underlying the two biological activities and the importance of a phenolic hydroxy group and its dimethylallylation for the structure‐based design of new functional properties of phenylpropenes.     

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.     

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).     

Cytotoxic and Melanogenesis‐Inhibitory Activities of Limonoids from the Leaves of Azadirachta indica (Neem)

Seventeen limonoids (tetranortriterpenoids), 1 – 17 , including three new compounds, i.e., 17‐defurano‐17‐(2,5‐dihydro‐2‐oxofuran‐3‐yl)‐28‐deoxonimbolide ( 14 ), 17‐defurano‐17‐(2ξ‐2,5‐dihydro‐2‐hydroxy‐5‐oxofuran‐3‐yl)‐28‐deoxonimbolide ( 15 ), and 17‐defurano‐17‐(5ξ‐2,5‐dihydro‐5‐hydroxy‐2‐oxofuran‐3‐yl)‐2′,3′‐dehydrosalannol ( 17 ), were isolated from an EtOH extract of the leaf of neem (Azadirachta indica). The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK‐BR‐3) cancer cell lines, seven compounds, i.e., 1 – 3, 12, 13, 15 , and 16 , exhibited potent cytotoxicities with IC₅₀ values in the range of 0.1–9.9 μM against one or more cell lines. Among these compounds, cytotoxicity of nimonol ( 1 ; IC₅₀ 2.8 μM ) against HL60 cells was demonstrated to be mainly due to the induction of apoptosis by flow cytometry. Western blot analysis suggested that compound 1 induced apoptosis via both the mitochondrial and death receptor‐mediated pathways in HL60 cells. In addition, when compounds 1 – 17 were evaluated for their inhibitory activities against melanogenesis in B16 melanoma cells, induced with α‐melanocyte‐stimulating hormone (α‐MSH), seven compounds, 1, 2, 4 – 6, 15 , and 16 , exhibited inhibitory activities with 31–94% reduction of melanin content at 10 μM concentration with no or low toxicity to the cells (82–112% of cell viability at 10 μM ). All 17 compounds were further evaluated for their inhibitory effects against the Epstein? Barr virus early antigen (EBV‐EA) activation induced by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in Raji cells.     

Optimization of Insecticidal Triterpene Derivatives by Biomimetic Oxidations with Hydrogen Peroxide and Iodosobenzene Catalyzed by MnIII and FeIII Porphyrin Complexes

Semisynthetic functionalized triterpenes (4α,14‐dimethyl‐5α,8α‐8,9‐epoxycholestan‐3β‐yl acetate; 4α,14‐dimethyl‐5α‐cholest‐8‐ene‐3,7,11‐trione; 4α,14‐dimethyl‐5α‐cholesta‐7,9(11)‐dien‐3‐one and 4α,14‐dimethyl‐5α‐cholest‐8‐en‐3β‐yl acetate), previously prepared from 31‐norlanostenol, a natural insecticide isolated from the latex of Euphorbia officinarum, have been subjected to oxidation with hydrogen peroxide (H₂O₂) and iodosobenzene (PhIO) catalyzed by porphyrin complexes (cytochrome P‐450 models) in order to obtain optimized derivatives with high regioselectivity. The main transformations were epoxidation of the double bonds and hydroxylations of non‐activated C–H groups and the reaction products were 25‐hydroxy‐4α,14‐dimethyl‐5α‐cholesta‐7,9(11)‐dien‐3β‐yl acetate (59 %), 25‐hydroxy‐4α,14‐dimethyl‐5α‐cholest‐8‐ene‐3,7,11‐trione (60 %), 4α,14‐dimethyl‐5α,7β‐7,8‐epoxycholest‐9(11)‐en‐3‐one (22 %), 8‐hydroxy‐4α,14‐dimethyl‐5α‐cholest‐9(11)‐ene‐3,7‐dione (16 %), 12α‐hydroxy‐4α,14‐dimethyl‐5α,7β‐7,8‐epoxycholest‐9(11)‐en‐3‐one (16 %), and 4α,14‐dimethyl‐5α,8α‐8,9‐epoxycholestan‐3β‐yl acetate (26 %), respectively. We also investigated the insect (Myzus persicae, Rhopalosiphum padi and Spodoptera littoralis) antifeedant and postingestive effects of these terpenoid derivatives. None of the compounds tested had significant antifeedant effects, however, all were more effective postingestive toxicants on S. littoralis larvae than the natural compound 31‐norlanostenol, with 4α,14‐dimethyl‐5α,8α‐8,9‐epoxycholestan‐3β‐yl acetate being the most active. The study of their structure–activity relationships points out at the importance of C3 and C7 substituents.     

Synthesis of a Natural Chalcone and Its Prenyl Analogs – Evaluation of Tumor Cell Growth‐Inhibitory Activities,and Effects on Cell Cycle and Apoptosis

Six prenyl (=3‐methylbut‐2‐en‐1‐yl) chalcones (=1,3‐diphenylprop‐2‐en‐1‐ones), 2 – 7 , and one natural non‐prenylated chalcone, 1 , have been synthesized and evaluated for their in vitro growth‐inhibitory activity against three human tumor cell lines. A pronounced dose‐dependent growth‐inhibitory effect was observed for all prenylated derivatives, except for 7 . The chalcone possessing one prenyloxy group at C(2′), i.e., 2 , was the most active derivative against the three human tumor cell lines (5.9<GI₅₀<7.7 μM ). The majority of compounds caused an increase in percentage of apoptotic cells and/or they interfered with cell cycle distribution in the MCF‐7 cell line.     

Phenolic compounds from Selaginella moellendorfii

Chemical investigation of the leaves and roots of Selaginella moellendorfii Hieron has resulted in the isolation and characterization of two new flavone glucosides, 7‐O‐(β‐glucopyranosyl(1→2)‐[β‐glucopyranosyl(1→6)]‐β‐glucopyranosyl)flavone‐3′,4′,5,7‐tetraol ( 1 ) and 7‐O‐(β‐glucopyranosyl(1→2)‐[β‐glucopyranosyl(1→6)]‐β‐glucopyranosyl)flavone‐4′,5,7‐triol ( 2 ), two new biflavonoids, 2,3‐dihydroflavone‐5,7,4′‐triol‐(3′→8″)‐flavone‐5″,6″,7″,4′′′‐tetraol ( 3 ) and 6‐methylflavone‐5,7,4′‐triol‐(3′→O→4′′′)‐6″‐methylflavone‐5″,7″‐diol ( 4 ), two new lignans, (7′E)‐3,5,3′,5′‐tetramethoxy‐8 : 4′‐oxyneolign‐7′‐ene‐4,9,9′‐triol ( 5 ) and 3,3′‐dimethoxylign‐8′‐ene‐4,4′,9‐triol ( 6 ), together with two known monolignans, four known lignans, and four known biflavonoids. Their structures were established by spectroscopic means and by comparison with literature values.     

New Steroids from the South China Sea Soft Coral Lobophytum sp.

Two new steroids, (22R,23S)‐3β‐hydroxy‐23‐methyl‐17,20‐epoxyergost‐5‐en‐22‐yl acetate and (22R,23S)‐5‐hydroperoxy‐23‐methyl‐5α‐17,20‐epoxyergost‐6‐ene‐3β,22‐diol, were isolated from the South China Sea soft coral Lobophytum sp., together with two related known ones. The structures of all compounds were elucidated by extensive spectroscopic analysis and by comparing their spectral data with those previously reported. The structure of (22R,23S)‐3β‐hydroxy‐23‐methyl‐17,20‐epoxyergost‐5‐en‐22‐yl acetate was further confirmed through chemical correlation. All the isolates were evaluated for the in vitro inhibitory activity against NF‐κB, a potential target for the treatment of cancer, and (22R,23S)‐5‐hydroperoxy‐23‐methyl‐5α‐17,20‐epoxyergost‐6‐ene‐3β,22‐diol exhibited moderate inhibition activity with IC₅₀ value of 8.96 μg/mL.     

Dehalogenation Activity of Selected Fungi Toward δ‐Iodo‐γ‐Lactone Derived from trans,trans‐Farnesol

Time‐course of biotransformation of racemic trans‐4‐((E)‐4′,8′‐dimethylnona‐3′,7′‐dien‐1‐yl)‐5‐iodomethyl‐4‐methyldihydrofuran‐2‐one ( 1 ) in fungal and yeast cultures was investigated. In these conditions, the substrate 1 was enantioselectively dehalogenated yielding 4‐((E)‐4′,8′‐dimethylnona‐3′,7′‐dien‐1‐yl)‐4‐methyl‐5‐methylenedihydrofuran‐2‐one ( 2 ) and its structure was established based on the spectroscopic data. The most effective biocatalyst used was Didymosphaeria igniaria, which catalyzed the process with highest rate and enantioselectivity (ee of product = 76%). The antiproliferative activity of δ‐iodo‐γ‐lactone 1 , product of its biotransformation 2 , and starting substrate (farnesol) were evaluated toward two cancer cell lines: A549 (human lung adenocarcinoma) and HL‐60 (human promyelocytic leukemia).     

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.     

Novel Neolignan from Penthorum chinense

A new neolignan （7＇E）-2＇,4,8-trihydroxy-3-methoxy-2,4＇-epoxy-8,5＇-neolign-7＇-en-7-one （1） was isolated from the whole plants of Penthorum chinense Pursh, along with Iupeol （2）, betulinic acid （3）, glyceryl monopalmitate （4）, β-sitosterol （5）, palmitic acid （5）, ursolic acid （7）, 2β,3β,23-trihydroxy-urs-12-ene-28-oic acid （8）, glyceryl monolaurate （9）, scopoletin （10）, （-）syringaresinol （11）, 9,9＇-O-diferuIoyl-（-）-secoisolariciresionl （12）, pinocembrin （13）, apigenin （14）, kaempferol （15）, Iuteolin （16）, β-daucosterol （17）, quercetin （18）, 1-O-（β-D-glucopyranosyl）-（2S, 2＇R, 3R,4E,8E）-2-（2＇-hydroxyhexadecanoy- lamino）-4,8-octdecadiene-1,3-diol （19）, gallic acid （20）, pinocembrin-7-O-β-D-glucoside （21）, and quercetin-3-O-β-D- glucoside （22）. The structures of these compounds were elucidated on the basis of chemical and spectral evidence.     

Cytotoxic Steroidal Saponins from the Rhizomes of Tacca integrifolia

Three new steroid saponins (3β,25R)‐spirost‐5‐en‐3‐yl 6‐deoxy‐α‐L ‐mannopyranosyl‐(1→2)‐[β‐D ‐glucopyranosyl‐(1→4)‐6‐deoxy‐α‐L ‐mannopyranosyl‐(1→3)]‐β‐D ‐glucopyranoside ( 1 ), (3β,22R,25R)‐26‐(β‐D ‐glucopyranosyloxy)‐22‐hydroxyfurost‐5‐en‐3‐yl 6‐deoxy‐α‐L ‐mannopyranosyl‐(1→2)‐[6‐deoxy‐α‐L ‐mannopyranosyl‐(1→3)]‐β‐D ‐glucopyranoside ( 3 ), and (3β,22R,25R)‐26‐(β‐D ‐glucopyranosyloxy)‐22‐hydroxyfurost‐5‐en‐3‐yl 6‐deoxy‐α‐L ‐mannopyranosyl‐(1→2)‐[β‐D ‐glucopyranosyl‐(1→4)‐6‐deoxy‐α‐L ‐mannopyranosyl‐(1→3)]‐β‐D ‐glucopyranoside ( 5 ), as well as the new pregnane glycoside (3β,16β)‐3‐{[6‐deoxy‐α‐L ‐mannopyranosyl‐(1→2)‐[6‐deoxy‐α‐L ‐mannopyranosyl‐(1→3)]‐β‐D ‐glucopyranosyl]oxy}‐20‐oxopregn‐5‐en‐16‐yl (4R)‐5‐(β‐D ‐glucopyranosyloxy)‐4‐methylpentanoate ( 6 ), were isolated from the rhizomes of Tacca integrifolia together with two known (25R) configurated steroid saponins (3β,25R)‐spirost‐5‐en‐3‐yl 6‐deoxy‐α‐L ‐mannopyranosyl‐(1→2)‐[6‐deoxy‐α‐L ‐mannopyranosyl‐(1→3)]‐β‐D ‐glucopyranoside ( 2 ) and (3β,22R,25R)‐26‐(β‐D ‐glucopyranosyloxy)‐22‐methoxyfurost‐5‐en‐3‐yl 6‐deoxy‐α‐L ‐mannopyranosyl‐(1→2)‐[6‐deoxy‐α‐L ‐mannopyranosyl‐(1→3)]‐β‐D ‐glucopyranoside ( 4 ). The cytotoxic activity of the isolated compounds was evaluated in HeLa cells and showed the highest cytotoxicity value for compound 2 with an IC₅₀ of 1.2±0.4 μM . Intriguingly, while compounds 1 – 5 exhibited similar cytotoxic properties between 1.2±0.4 ( 2 ) and 4.0±0.6 μM ( 5 ), only compound 2 showed a significant microtubule‐stabilizing activity in vitro.     

Regioselective hydroxylation of daidzein using P450 (CYP105D7) from Streptomyces avermitilis MA4680

Regiospecific 3′‐hydroxylation reaction of daidzein was performed with CYP105D7 from Streptomyces avermitilis MA4680 expressed in Escherichia coli. The apparent K_m and k_cat values of CYP105D7 for daidzein were 21.83 ± 6.3 µM and 15.01 ± 0.6 min^?1 in the presence of 1 µM of CYP105D7, putidaredoxin (CamB) and putidaredoxin reductase (CamA), respectively. When CYP105D7 was expressed in S. avermitilis MA4680, its cytochrome P450 activity was confirmed by the CO‐difference spectra at 450 nm using the whole cell extract. When the whole‐cell reaction for the 3′‐hydroxylation reaction of daidzein was carried out with 100 µM of daidzein in 100 mM of phosphate buffer (pH 7.5), the recombinant S. avermitilis grown in R2YE media overexpressing CYP105D7 and ferredoxin FdxH (SAV7470) showed a 3.6‐fold higher conversion yield (24%) than the corresponding wild type cell (6.7%). In a 7 L (working volume 3 L) jar fermentor, the recombinants S. avermitilis grown in R2YE media produced 112.5 mg of 7,3′,4′‐trihydroxyisoflavone (i.e., 29.5% conversion yield) from 381 mg of daidzein in 15 h. Biotechnol. Bioeng. 2010. 105: 697–704. © 2009 Wiley Periodicals.     

Cytotoxic and Apoptosis‐Inducing Activities of Steviol and Isosteviol Derivatives against Human Cancer Cell Lines

Seventeen steviol derivatives, i.e., 2 – 18 , and 19 isosteviol derivatives, i.e., 19 – 37 , were prepared from a diterpenoid glycoside, stevioside ( 1 ). Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK‐BR‐3) cancer cell lines, nine steviol derivatives, i.e., 5 – 9 and 11 – 14 , and five isosteviol derivatives, i.e., 28 – 32 , exhibited activities with single‐digit micromolar IC₅₀ values against one or more cell lines. All of these active compounds possess C(19)‐O‐acyl group, and among which, ent‐kaur‐16‐ene‐13,19‐diol 19‐O‐4′,4′,4′‐trifluorocrotonate ( 14 ) exhibited potent cytotoxicities against four cell lines with IC₅₀ values in the range of 1.2–4.1 μM . Compound 14 induced typical apoptotic cell death in HL60 cells upon evaluation of the apoptosis‐inducing activity by flow‐cytometric analysis. These results suggested that acylation of the 19‐OH group of kaurane‐ and beyerane‐type diterpenoids might be useful for enhancement of their cytotoxicities with apoptosis‐inducing activity.     

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.     

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 .     

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.