Phytoecdysteroids of Silene guntensis and their in vitro cytotoxic and antioxidant activity

Phytoecdysteroids from aerial parts of Silene guntensis B. Fedtsch were investigated and three phytoecdysteroids were isolated: 2,3-diacetate-22-benzoate-20-hydroxyecdysone (1), 2-deoxy-20-hydroxyecdysone (2), and 20-hydroxyecdysone (3). Their chemical structures were elucidated by DEPT, COSY, 1H and 13C NMR spectroscopy. The isolated compounds 1-3 and crude extracts were evaluated for their antiproliferative and antioxidant activities. They exhibited substantial inhibition of cell growth against human cervix adenocarcinoma (HeLa), hepatocellular carcinoma (HepG-2), and breast adenocarcinoma (MCF-7) cells. The chloroform extract showed potent cytotoxic effects [IC50 values (26.58 +/- 1.88) microg/mL, (20.99 +/- 1.64) microg/mL, and (18.89 +/- 2.36) microg/mL, respectively]. The new compound 1 was mildly cytotoxic compared to extracts [(127.97 +/- 11.34), (106.76 +/- 7.81), and (203.10 +/- 19.56) microg/mL, respectively]. Water and n-butanol extracts exhibited good antioxidant activities [IC50 values of (68.90 +/- 6.45) microg/mL and (69.12 +/- 5.85) microg/mL, respectively].     

Melanogenesis‐Inhibitory and Cytotoxic Activities of Chemical Constituents from the Leaves of Sauropus androgynus L. Merr. (Euphorbiaceae)

A new steroid, 20‐hydroxyisofucosterol (stigmasta‐5,24(28)‐diene‐3β,20β‐diol) ( 7 ), along with six known compounds 1 – 6 were isolated from the MeOH extract of the leaves of Sauropus androgynus L. Merr . (Euphorbiaceae). The structure of new steroid was determined by HR‐APCI‐MS and various NMR techniques in combination with literature data. Subsequently, their anti‐inflammatory, cytotoxic activities against five human cell lines, as well as inhibitory activities against the α‐MSH induced melanogenesis on the B16 cell line were evaluated. As the results, steroid compounds, 6 and 7 exhibited moderate cytotoxic to HL60, AZ521, SKBR3, and A549 tumor cell lines (IC₅₀ 26.9 – 45.1 μm ) with high tumor selectivity for A549 relative to WI38 cell lines (SI 2.6 and 3.0, resp.). And, flavonoid compounds, 4 and 5 exhibited superior inhibitory activities against melanogenesis (67.0 – 94.7% melanin content), even with no or low toxicity to the cells (90.1 – 99.6% cell viability) at the concentrations from 10 to 100 μm . Furthermore, Western blot analysis suggested that compound 5 could inhibit melanogenesis by suppressing the protein expressions of MITF, TRP‐1, TRP‐2, and tyrosinase.     

酒饼簕根中的细胞毒活性成分

用色谱技术从酒饼簕[Atalantia buxifolia(Poir.)Oliv.]根的乙醇提取物中分离得到9个化合物,经波谱分析与文献数据对照,分别鉴定为buxifoliadineA(1)、1,3-dihydroxy-2,4-diprenylacridone(2)、5-hydroxy-N-methylseverifoline(3)、buxifoliadine B(4)、N-methylatalaphylline(5)、atalaphylline(6)、东风桔碱(7)、葡萄内酯(8)和松柏醛(9)。化合物9为首次从酒饼簕根中分离得到。细胞毒活性测试结果表明,化合物1和8对人肝癌细胞(SMMC-7721)具有细胞毒活性,化合物3对慢性髓原白血病细胞(K562)的增殖显示了较强的生长抑制活性。     

Two New Steroids from an Endophytic Fungus Phomopsis sp.

Two new steroids, (14β,22E)‐9,14‐dihydroxyergosta‐4,7,22‐triene‐3,6‐dione ( 1 ) and (5α,6β,15β,22E)‐6‐ethoxy‐5,15‐dihydroxyergosta‐7,22‐dien‐3‐one ( 2 ), together with three known steroids, calvasterols A and B ( 3 and 4 , resp.), and ganodermaside D ( 5 ), were isolated from the culture broth of an endophytic fungus Phomopsis sp. isolated from Aconitum carmichaeli. The structures of these compounds were elucidated on the basis of spectroscopic analysis, and their inhibitory activities against six pathogenic fungi were evaluated. Most of the compounds showed moderate or weak antifungal activities in a broth‐microdilution assay.     

Biological Activities of Phenolics from the Fruits of Phyllanthus emblica L. (Euphorbiaceae)

Seven phenolic compounds, 1 – 7 , including a new organic acid gallate, mucic acid 1‐ethyl 6‐methyl ester 2‐O‐gallate ( 7 ), were isolated from the MeOH extract of the fruits of Phyllanthus emblica L. (Euphorbiaceae). The structures were elucidated on the basis of extensive spectroscopic analysis and comparison with literature data. Upon evaluated for their antioxidant abilities by 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH), 2,2′‐azinobis(3‐ethylbenzthiazoline‐6‐sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays. The inhibitory activities against melanogenesis in B16 melanoma cells induced by α‐MSH, as well as cytotoxic activities against four human cancer cell lines were also evaluated. All phenolic compounds, 1 – 7 , exhibited potent antioxidant abilities (DPPH: IC₅₀ 5.6 – 12.9 μm ; ABTS: 0.87 – 8.43 μm Trolox/μm ; FRAP: 1.01 – 5.79 μm Fe²⁺/μm , respectively). Besides, 5 – 7 , also exhibited moderate inhibitory activities against melanogenesis (80.7 – 86.8% melanin content), even with no or low toxicity to the cells (93.5 – 101.6% cell viability) at a high concentration of 100 μm . Compounds 1 – 3 exhibited cytotoxic activity against one or more cell lines (IC₅₀ 13.9 – 68.4%), and compound 1 with high tumor selectivity for A549 (SI 3.2).     

Limonoids and Flavonoids from the Flowers of Azadirachta indica var. siamensis,and Their Melanogenesis‐Inhibitory and Cytotoxic Activities

A new limonoid, 7‐O‐acetyl‐7‐O‐debenzoyl‐22‐hydroxy‐21‐methoxylimocinin ( 2 ), and two new flavonoids, 3′‐(3‐hydroxy‐3‐methylbutyl)naringenin ( 7 ) and 4′‐O‐methyllespedezaflavanone C ( 9 ), along with nine known compounds, including two limonoids, 1 and 3 , and seven flavonoids, 4 – 6, 8 , and 10 – 12 , were isolated from a MeOH extract of the flowers of Azadirachta indica A.Juss. var. siamensis Valeton (Siamese neem tree; Meliaceae). The structures of new compounds were elucidated on the basis of extensive spectroscopic analysis and comparison with literature data. All of these compounds were evaluated for their melanogenesis‐inhibitory activities in B16 melanoma cells induced with α‐melanocyte‐stimulating hormone (α‐MSH). Compound 2 (16.9% melanin content at 30 μM ), 6‐deacetylnimbin ( 3 ; 49.6% melanin content at 100 μM ), and kaempferide ( 10 ; 41.7% melanin content at 10 μM ) exhibited inhibitory effects with no, or almost no, toxicity to the cells (81.0–111.7% cell viability). In addition, evaluation of their cytotoxic activities against HL60, A549, AZ521, and SK‐BR‐3 human cancer cell lines, isoazadironolide ( 1 ), 4′‐O‐methyl‐8‐prenylnaringenin ( 5 ), euchrestaflavanone A ( 8 ), 9 , and 3‐methoxy‐3′‐prenylnaringenin ( 12 ) revealed potent cytotoxicities against one or more cell lines with IC₅₀ values in the range of 4.5–9.9 μM .     

Two New Sesquiterpene Derivatives from the Tunisian Endemic Ferula tunetana Pom.

A new sesquiterpene ester, tunetanin A ( 1 ), a new sesquiterpene coumarin, tunetacoumarin A ( 2 ), together with eight known compounds, i.e., coladin ( 3 ), coladonin ( 4 ), isosmarcandin ( 5 ), 13‐hydroxyfeselol ( 6 ), umbelliprenin ( 7 ) propiophenone ( 8 ), β‐sitosterol ( 9 ), and stigmasterol ( 10 ), were isolated from the roots of Ferula tunetana. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D‐ and 2D‐NMR experiments and MS analysis, as well as by comparison with published data. The cytotoxicity of compounds 1 – 7 towards two human colon cancer cell lines, HT‐29 and HCT 116, was evaluated. Compounds 3, 4 , and 6 showed weak cytotoxic activities.     

华麻花头根中的蜕皮甾酮类成分

从华麻花头(Serratula chinensis S．Moore)根中分得7种蜕皮甾酮类化合物,经光谱分析和化学方法,分别鉴定为：20-羟基蜕皮松(1),podecdysone C(2),3-氧-乙酰基-20-羟基蜕皮松(3),20-羟基蜕皮松-20,22．-缩丁醛(4),shidasterone(5),atrotosterone C(6)和carthamosterone(7),其中20-羟基蜕皮松-20,22．缩丁醛为一新的化合物。     

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.     

Polycyclic Polyprenylated Acylphloroglucinols and Chromone O‐Glucosides from Hypericum henryi subsp. uraloides

Two new C(30)‐epimeric polycyclic polyprenylated acylphloroglucinols (PPAPs), named uralodins B and C ( 1 and 2 , resp.), were isolated from the aerial parts of Hypericum henryi subsp. uraloides together with two new chromone glucosides, urachromones A and B ( 3 and 4 , resp.), as well as 16 known compounds. Their structures were established by extensive NMR techniques and MS analysis. The epimers 1 and 2 always behaved like a single compound when examined by TLC, and were separated by HPLC. Their configuration was distinguished by comparative analysis of the NMR data with known analogues together with the ROESY experiment. All the isolated PPAPs were evaluated for their cytotoxic activities against HepG2, SGC7901, HL‐60, and K562 cell lines. Compound 1 showed modest cytotoxic activities against SGC7901 and HL‐60 cell lines, and 2 showed modest cytotoxic activities against HepG2, SGC7901, HL‐60, and K562 cell lines.     

Salvisertin A,a New Hexacyclic Triterpenoid,and Other Bioactive Terpenes from Salvia deserta Root

Using various chromatographic methods, a new hexacyclic triterpenoid, 2β,3β,24β‐trihydroxy‐12,13‐cyclotaraxer‐l4‐en‐28oic acid ( 1 ), together with ten known compounds, 2α,3α,23‐trihydroxyurs‐12,20(30)‐dien‐28oic acid ( 2 ), 6,7‐dehydroroyleanone ( 3 ), horminone ( 4 ), 7‐O‐methylhorminone ( 5 ), sugiol ( 6 ), demethylcryptojaponol ( 7 ), 14‐deoxycoleon U ( 8 ), 5,6‐didehydro‐7‐hydroxy‐taxodone ( 9 ), ferruginol ( 10 ), and dichroanone ( 11 ), were isolated from the roots of Salvia deserta. Their structures were identified on the basis of spectroscopic analysis and comparison with the reported data. The individual compounds ( 1 , 3  –  8 ) were screened for cytotoxic activity, using the sulforhodamine B bioassay (SRB) method. As the results, Compounds 3 , 5 , and 8 showed cytotoxic potency against A549, MDA‐MB‐231, KB, KB‐VIN, and MCF7 cell lines with IC₅₀ values ranging from 6.5 to 10.2 μm .     

Eudesmanolides and Other Constituents from the Flowers of Wedelia trilobata

Two eudesmane sesquiterpene lactones, wedetrilides B ( 1 ) and C ( 2 ), along with five known analogues ( 3 – 8 ), an ent‐kaurane diterpenoid ( 9 ), a steroid ( 10 ), as well as cinnamic acid derivatives ( 11 – 13 ), were isolated from the flowers of Wedelia trilobata. Their structures were elucidated on the basis of extensive spectroscopic analyses and by comparison of their NMR data with those of related compounds. Furthermore, the structures of 1 and 3 – 5 were confirmed by X‐ray single‐crystal diffraction analyses. Compounds 4 and 5 exhibited weak cytotoxic activities against the MCF‐7, HeLa, and A549 cell lines. Compounds 3 – 5 were also evaluated for their inhibitory effects against HIV lytic replication.     

Chemical Constituents of Primulina eburnea (Gesneriaceae) and Their Cytotoxic Activities

Two new ursane-type triterpenes, eburnealactones A and B ( 1 and 2 ), one new flavonoid, eburneatin A ( 6 ), and one new phenylethanoid glycoside, chiritoside D ( 7 ), along with 9 known compounds ( 3–5 , 8–13 ) were isolated from the whole plant of Primulina eburnea. Their structures were elucidated by comprehensive spectroscopic data analysis (IR, UV, NMR, and HR-ESI-MS). All the compounds were evaluated for their cytotoxic activities. Compound 1 showed significant cytotoxic activities against MKN-45 cell lines and 5637 cell lines with the IC₅₀ values of 9.57 μM and 8.30 μM, respectively. Compound 1 exhibited moderate cytotoxic activities against A549 and PATU8988T cell lines with the IC₅₀ values of 30.70 μM and 38.22 μM, respectively. Compound 6 exhibited moderate cytotoxic activities against MKN-45, HCT116, PATU8988T, 5637 and A-673 cell lines with the IC₅₀ values of 19.69 μM, 16.44 μM, 18.07 μM, 11.51 μM and 18.15 μM, respectively. Compound 5 showed moderate cytotoxic activities against A549 cell lines with the IC₅₀ values of 24.06 μM.     

Isolation and identification of major ecdysteroids from the pycnogonidPycnogonum litorale (Ström) (Arthropoda,Pantopoda)

Summary From adults ofPycnogonum litorale (Ström) eight ecdysteroids were isolated by HPLC and identified by mass spectrometry and NMR. One of the compounds is 20-hydroxyecdysone, two further ecdysteroids show no OH-group at C-22 (22-deoxy-20,26-dihydroxyecdysone, 22-deoxy-20-hydroxyecdysone=taxisterone). The five other compounds are esters of ecdysteroids with acetic acid (25R and 25S isomers of 20,26-dihydroxyecdysone 22-acetate, 20-hydroxyecdysone 22-acetate) or with glycolic acid (20-hydroxyecdysone 22-glycolate, ecydsone 22-glycolate). The latter are new among zoo- and phytoecdysteroids. No significant amounts of ecdysone could be detected. The origin of the ecdysteroids inPycnogonum litorale and their biological activity are discussed.Abbreviations RP-HPLC Reversed-phase high performance liquid chromatography - NP normal phase - RIA radioimmunoassay - NMR nuclear magnetic resonance - FT Fourier transform - CI/D chemical ionization/desorption - TFA trifluoroacetic acid - E ecdysone - 20E 20-hydroxyecdysone - 2026E 20 26-dihydroxyecdysone     

New Derivatives of Nonactic and Homononactic Acids from Bacillus pumilus Derived from Breynia fruticosa

Six new nonactic and homononactic acid derivatives, ethyl homononactate ( 1 ), ethyl nonactate ( 2 ), homononactyl homononactate ( 6 ), ethyl homononactyl nonactate ( 7 ), ethyl homononactyl homononactate ( 8 ), and ethyl nonactyl nonactate ( 9 ), as well as four known compounds, homononactic acid ( 3 ), nonactic acid ( 4 ), homononactyl nonactate ( 5 ), and bishomononactic acid ( 10 ), were isolated from culture broth of Bacillus pumilus derived from Breynia fruticosa. The structures of new compounds were elucidated by spectroscopic analysis and chemical methods. The optical purities of 1 – 6 were determined by HPLC/MS after treatment with L ‐phenylalanine methyl ester. The dimeric compounds 5 – 9 showed weak cytotoxic activities against five human cancer cell lines (IC₅₀ 19–100 μg/ml).     

Melanogenesis‐Inhibitory Saccharide Fatty Acid Esters and Other Constituents of the Fruits of Morinda citrifolia (Noni)

Five new saccharide fatty acid esters, named nonioside P ( 3 ), nonioside Q ( 4 ), nonioside R ( 8 ), nonioside S ( 10 ), and nonioside T ( 14 ), and one new succinic acid ester, butyl 2‐hydroxysuccinate (=4‐butoxy‐3‐hydroxy‐4‐oxobutanoic acid) ( 31 ), were isolated, along with 26 known compounds, including eight saccharide fatty acid esters, 1, 2, 5, 6, 7, 9, 12 , and 13 , three hemiterpene glycosides, 15, 17 , and 18 , six iridoid glycosides, 21 – 25 , and 27 , and nine other compounds, 20, 28, 29 , and 32 – 37 , from a MeOH extract of the fruit of Morinda citrifolia (noni). Upon evaluation of these and five other glycosidic compounds, 11, 16, 19, 26 , and 30 , from M. citrifolia fruit extract for their inhibitory activities against melanogenesis in B16 melanoma cells induced with α‐melanocyte‐stimulating hormone (α‐MSH), most of the saccharide fatty acid esters, hemiterpene glycosides, and iridoid glycosides showed inhibitory effects with no or almost no toxicity to the cells. These compounds were further evaluated with respect to their cytotoxic activities against two human cancer cell lines (HL‐60 and AZ521) and their inhibitory effects on Epstein? Barr virus early antigen (EBV‐EA) activation induced with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in Raji cells.     

Triterpenoid Saponins with Potential Cytotoxic Activities from the Root Bark of Ilex rotunda Thunb.

A new 19‐oxo‐18,19‐seco‐ursane‐type triterpeonoid saponin, laevigin E ( 8 ), together with 17 known compounds ( 1 – 7 and 9 – 18 ) were isolated from the root bark of Ilex rotunda Thunb . Their structures were determined by various spectroscopic analysis. Among them, compounds 6 , 9 , 11 , and 18 were isolated from this species for the first time, while compounds 10 and 12 were firstly isolated from the family Aquifoliaceae. Biological activity assay showed that all triterpenoids exhibit moderate cytotoxic activities against MCF7, A549, HeLa and LN229 cell lines. The four triterpenoid saponins ( 3 , 4 , 6 , and 8 ) exhibit slightly better activities compared to the four triterpenoid sapogenins ( 1 , 2 , 5 , and 7 ). Compound 8 showed the best cytotoxicity against A549, HeLa and LN229 cell lines with IC₅₀ of 17.83, 22.58 and 30.98 μm , respectively.     

Phloroglucinol Derivatives from the Fruits of Eucalyptus globulus and Their Cytotoxic Activities

A new phloroglucinol derivative, named eucalyptin B ( 1 ), along with five related known compounds ( 2 – 6 ), was isolated from the fruits of Eucalyptus globulus. Their structures were elucidated by means of 1D‐ and 2D‐NMR spectroscopy, with the absolute configuration of 1 determined by electronic circular dichroism (ECD) calculations. All isolated compounds ( 1 – 6 ) were evaluated for their cytotoxic activities against lung (A549), breast (4T1), and skin (B16F10) cancer cell lines. On the basis of cell viability assay, the cytotoxic activity of eucalyptin B ( 1 ) was further confirmed by apoptosis assay. Additionally, after treatment with eucalyptin B ( 1 ), the apoptosis factor proteins (Bcl2 and Bax) and caspase‐3 levels in A549 cells were also determined by Western‐blot analysis. By cytotoxic assay, eucalyptin B ( 1 ) exhibited potent cytotoxicity against A549 cells with an IC₅₀ value of 1.51 μm and induced concentration dependent apoptosis of up to 49%. Additionally, eucalyptin B ( 1 ) inhibited 5‐fold and increased 10‐folds in the level of Bcl2 and Bax, respectively. Furthermore, the 11‐fold increase in the level of caspase‐3 confirmed eucalyptin B ( 1 ) activated caspase dependent apoptosis pathway. In conclusion, the isolated compound eucalyptin B ( 1 ) has promising cytotoxic activity in tumor cells, especially in A549.     

Cytotoxic Activity and Related Mechanisms of Prenylflavonoids Isolated from Mallotus conspurcatus Croizat

Five prenylflavonoids, 6‐prenylnaringenin ( 1 ), 8‐prenylnaringenin ( 2 ), 7‐O‐methyl‐8‐prenylnaringenin ( 3 ), 7‐O‐methyl‐6‐prenylnaringenin ( 4 ), and 4′‐O‐methyl‐6‐prenylnaringenin ( 5 ), were isolated from the traditional herb Mallotus conspurcatus Croizat (Euphorbiaceae). Compounds 1 – 5 revealed cytotoxic activity against cervical cancer (HeLa) cells with IC₅₀ values ranging from 10.08 to 60.16 μm by MTT method, and interestingly, these prenylflavonoids were less toxic to normal HL‐7702 cells. Furthermore, compounds 1 and 5 could inhibit the c‐myc expression and telomerase activity and cause mitochondrial dysfunction. These findings might contribute to a better understanding of the biological activities of prenylflavonoids and lay the foundation for further studies on the cytotoxic activity of natural products isolated from M. conspurcatus.     

Drimane Sesquiterpenoids from the Aspergillus oryzae QXPC‐4

Three new drimane sesquiterpenoids, astellolides C–E ( 1 – 3 , resp.), four new drimane sesquiterpenoid p‐hydroxybenzoates, astellolides F–I ( 4 – 7 , resp.), together with two known compounds astellolides A and B ( 8 and 9 , resp.), have been isolated from the liquid culture of Aspergillus oryzae (strain No. QXPC‐4). Their structures were established by comprehensive analysis of spectroscopic data. The relative and absolute configurations were determined on the basis of NOESY and CD data, together with single‐crystal X‐ray diffraction analyses of compounds 1 – 3 . The metabolites were evaluated for their cytotoxic activities, however, no compounds showed a significant cytotoxicity against the tested cell lines at a concentration of 20 μM .