Triterpene Glucosides from the Leaves of Aralia elata and Their Cytotoxic Activities

Three new triterpene glucosides, named congmuyenosides C–E ( 1 – 3 , resp.), along with four known ones, were isolated from an EtOH extract of Aralia elata (Miq .) Seem . leaves. The structures of the new compounds were identified as 3‐O‐{β‐D ‐glucopyranosyl‐(1→3)‐β‐D ‐glucopyranosyl‐(1→3)‐[β‐D ‐glucopyranosyl‐(1→2)]‐β‐D ‐glucopyranosyl}caulophyllogenin ( 1 ), 3‐O‐{β‐D ‐glucopyranosyl‐(1→3)‐β‐D ‐glucopyranosyl‐(1→3)‐[β‐D ‐glucopyranosyl‐(1→2)]‐β‐D ‐glucopyranosyl}hederagenin 28‐O‐β‐D ‐glucopyranosyl ester ( 2 ), 3‐O‐{β‐D ‐glucopyranosyl‐(1→3)‐β‐D ‐glucopyranosyl‐(1→3)‐[β‐D ‐glucopyranosyl‐(1→2)]‐β‐D ‐glucopyranosyl}echinocystic acid 28‐O‐β‐D ‐glucopyranosyl ester ( 3 ) on the basis of spectral analyses, including MS, ¹H‐NMR, ¹³C‐NMR, DEPT, HSQC, HMBC, NOESY, and HSQC‐TOCSY experiments. All isolates obtained were evaluated for their cytotoxic activities against three human tumor cell lines (HepG2, SKOV3, and A549). Compound 3 showed significant cytotoxicity against A549 cell line (IC₅₀ 9.9±1.5 μM ).     

Cytotoxic and Antimicrobial Activity of Dehydrozingerone based Cyclopropyl Derivatives

A small series of 1‐acetyl‐2‐(4‐alkoxy‐3‐methoxyphenyl)cyclopropanes was prepared, starting from dehydrozingerone (4‐(4‐hydroxy‐3‐methoxyphenyl)‐3‐buten‐2‐one) and its O‐alkyl derivatives. Their microbiological activities toward some strains of bacteria and fungi were tested, as well as their in vitro cytotoxic activity against some cancer cell lines (HeLa, LS174 and A549). All synthesized compounds showed significant antimicrobial activity and expressed cytotoxic activity against tested carcinoma cell lines, but they showed no significant influence on normal cell line (MRC5). Butyl derivative is the most active on HeLa cells (IC₅₀ = 8.63 μm ), while benzyl one is active against LS174 and A549 cell lines (IC₅₀ = 10.17 and 12.15 μm , respectively).     

Cytotoxic Tetraprenylated Alkaloids from the South China Sea Gorgonian Euplexaura robusta

Nine achiral tetraprenylated alkaloids, including three new compounds, named malonganenones I–K ( 1 – 3 , resp.), together with six known analogs, 4 – 9 , were isolated from the gorgonian Euplexaura robusta collected from Weizhou Island of Guangxi Province, China. The structures of compounds 1 – 3 were elucidated by extensive spectral analyses, especially of their 1D‐ and 2D‐NMR data. Compounds 1, 4, 6 , and 7 showed moderate cytotoxicities against K562 and HeLa tumor cell lines with IC₅₀ values ranging from 0.35 to 10.82 μM . Compound 6 also showed moderate inhibitory activity against c‐Met kinase at a concentration of 10 μM .     

Three New Phenylpropanoids from the Roots of Piper taiwanense and Their Inhibitory Activities on Platelet Aggregation and Mycobacterium tuberculosis

Bioassay‐guided fractionation of the active AcOEt‐soluble fraction from the roots of Piper taiwanense has led to the isolation of two new phenylpropanoids, taiwanensols A and B ( 1 and 2 , resp.), a new natural product, taiwanensol C ( 3 ), and 3‐acetoxy‐4‐hydroxy‐1‐allylbenzene ( 4 ). The compounds were obtained as two isomer mixtures ( 1 / 2 and 3 / 4 , resp.). Their structures were elucidated by spectroscopic analyses, including 1D‐ and 2D‐NMR spectroscopy and mass spectrometry, and by the comparison of their NMR data with those of related compounds. Compounds 1 – 4 were evaluated for their antiplatelet and antitubercular activities. The mixtures 1 / 2 and 3 / 4 showed potent inhibitory activities against platelet aggregation induced by collagen, with IC₅₀ values of 35.2 and 8.8 μM , respectively. In addition, 1 / 2 and 3 / 4 showed antitubercular activities against Mycobacterium tuberculosis H37Rv, with MIC values of 30.0 and 48.0 μg/ml, respectively.     

Triterpene Saponins from the Roots of Ilex asprella

Six new triterpene saponins, ilexasprellanosides A–F ( 1 – 6 , resp.), together with eleven known compounds were isolated from the roots of Ilex asprella. The new saponins were characterized as ursa‐12,18‐dien‐28‐oic acid 3‐O‐β‐D ‐xylopyranoside ( 1 ), 19α‐hydroxyursolic acid 3‐O‐β‐D ‐(2′‐O‐acetylxylopyranoside) ( 2 ), 19α‐hydroxyursolic acid 3‐O‐β‐D ‐glucuronopyranoside ( 3 ), 3β,19α‐dihydroxyolean‐12‐en‐23,28‐dioic acid 28‐O‐β‐D ‐glucopyranoside ( 4 ), 19α‐hydroxyoleanolic acid 3‐O‐β‐D ‐(2′‐O‐acetylxylopyranoside) ( 5 ), 19α‐hydroxyoleanolic acid 3‐O‐β‐D ‐glucuronopyranoside ( 6 ). The structures of the new compounds were elucidated by analysis of their spectroscopic data and chemical degradation. Compounds 2, 4 , oleanolic acid 3‐O‐β‐D ‐glucuronopyranoside, 3‐β‐acetoxy‐28‐hydroxyurs‐12‐ene, and pomolic acid showed significant cytotoxic activities against human tumor cell line A549 (IC₅₀ values of 1.87, 2.51, 1.41, 3.24, and 5.63 μM , resp.).     

Inhibition of NO Production by Grindelia argentina and Isolation of Three New Cytotoxic Saponins

A bioassay‐guided phytochemical analysis of the ethanolic extract of Grindelia argentina Deble & Oliveira ‐Deble (Asteraceae) allowed the isolation of a known flavone, hispidulin, and three new oleanane‐type saponins, 3‐O‐β‐D ‐xylopyranosyl‐(1→3)‐β‐D ‐glucopyranosyl‐2β,3β,16α,23‐tetrahydroxyolean‐12‐en‐28‐oic acid 28‐O‐β‐D ‐xylopyranosyl‐(1→2)‐β‐D ‐apiofuranosyl‐(1→3)‐β‐D ‐xylopyranosyl‐(1→3)‐α‐L ‐rhamnopyranosyl‐(1→2)‐α‐L ‐arabinopyranosyl ester ( 2 ), 3‐O‐β‐D ‐glucopyranosyl‐2β,3β,23‐trihydroxyolean‐12‐en‐28‐oic acid 28‐O‐β‐D ‐xylopyranosyl‐(1→2)‐β‐D ‐apiofuranosyl‐(1→3)‐β‐D ‐xylopyranosyl‐(1→3)‐α‐L ‐rhamnopyranosyl‐(1→2)‐α‐L ‐arabinopyranosyl ester, ( 3 ) and 3‐O‐β‐D ‐xylopyranosyl‐(1→3)‐β‐D ‐glucopyranosyl‐2β,3β,23‐trihydroxyolean‐12‐en‐28‐oic acid 28‐O‐β‐D ‐xylopyranosyl‐(1→2)‐β‐D ‐apiofuranosyl‐(1→3)‐β‐D ‐xylopyranosyl‐(1→3)‐α‐L ‐rhamnopyranosyl‐(1→2)‐α‐L ‐arabinopyranosyl ester ( 4 ), named grindeliosides A–C, respectively. Their structures were determined by extensive 1D‐ and 2D‐NMR experiments along with mass spectrometry and chemical evidence. The isolated compounds were evaluated for their inhibitory activities against LPS/IFN‐γ‐induced NO production in RAW 264.7 macrophages and for their cytotoxic activities against the human leukemic cell line CCRF‐CEM and MRC‐5 lung fibroblasts. Hispidulin markedly reduced LPS/IFN‐γ‐induced NO production (IC₅₀ 51.4 μM ), while grindeliosides A–C were found to be cytotoxic, with grindelioside C being the most active against both CCRF‐CEM (IC₅₀ 4.2±0.1 μM ) and MRC‐5 (IC₅₀ 4.5±0.1 μM ) cell lines.     

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.     

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.     

Characteristic Steroids from the South China Sea Gorgonian Muricella sibogae and Their Cytotoxicities

Twenty‐four steroid‐based natural products, 9,10‐secosteroids ( 1 – 10 ), 1,4‐dien‐3‐one steroids ( 11 – 19 ), and 4‐en‐3‐one steroids ( 20 – 24 ), containing varying side‐chains, were isolated from the South China Sea gorgonian Muricella sibogae. The structures of one new 9,10‐secosteroid, sibogol D ( 1 ), and two new 1,4‐dien‐3‐one steroids, sibogols E and F ( 11 and 12 ), were elucidated by extensive spectroscopic analyses and by comparison with the literature data. Cytotoxicities for all the isolates were evaluated against four selected tumor cell lines, HL‐60, HCT116, K562, and P388. Compounds 3, 9 , and 13 exhibited potent cytotoxic activities against the HL‐60 cell line, with IC₅₀ values ranging from 1.27 to 10.05 μM , and compound 3 was also cytotoxic against HCT116 with an IC₅₀ value of 5.8 μM . The bioassay results also indicated a potential relationship between structural patterns and activity. The newly presented series of 1,4‐dien‐3‐one and 4‐en‐3‐one types of steroids relating to the unique 9,10‐secosteroids in biogenesis were found in this species for the first time, which is of considerable chemotaxonomic significance.     

Two New Dolabrane Diterpenes from the Chinese Mangrove Ceriops tagal

Two new dolabrane diterpenes, tagalenes J and K ( 1 and 2 ), together with eleven known analogues ( 3 – 13 ), were isolated from the ethanolic extract of the Chinese mangrove Ceriops tagal. The structures of these compounds were determined by extensive spectroscopic analysis, including 1D‐, 2D‐NMR and HR‐ESI‐MS, as well as the comparison with data in the literatures. Cytotoxicities of isolated compounds against MCF‐7, SW480, HepG2, HeLa, PANC‐1, and A2058 cancer cell lines were also evaluated. Compound 4 exhibited weak cytotoxic activity against SW480, HeLa, and PANC‐1 cell lines with IC₅₀ values of 27.7, 22.2, and 17.6 μm , respectively.     

New Bioactive Macrocyclic Diterpenoids from Euphorbia helioscopia

Three new macrocyclic diterpenoids, euphoscopoids A – C ( 1 – 3 ), including two new jatrophanes and a new lathyrane, were isolated from the whole plant of Euphorbia helioscopia. Their structures were elucidated by spectroscopic methods. Antifeedant and cytotoxic activities of these isolates were evaluated. All compounds showed significant antifeedant activity against a generalist plant‐feeding insect, Helicoverpa armigera, with EC₅₀ values ranging from 2.05 to 4.34 μg/cm². In addition, compound 2 showed moderate cytotoxicity against tumor cell lines NCI‐H1975, HepG2, and MCF‐2, while compounds 1 and 3 were not active at 80 μm . The results suggested not only the defensive function of macrocyclic diterpenoids in E. helioscopia against insect herbivores, but also their potential applications as new natural insect antifeedants.     

A New DNA‐Intercalative Cytotoxic Allylic Xanthone from Swertia corymbosa

Phytochemical investigation of the CHCl₃ fraction of Swertia corymbosa resulted in the isolation of a new 3‐allyl‐2,8‐dihydroxy‐1,6‐dimethoxy‐9H‐xanthen‐9‐one ( 1 ), along with four known xanthones, gentiacaulein ( 3 ), norswertianin ( 4 ), 1,3,6,8‐tetrahydroxyxanthone ( 5 ), and 1,3‐dihydroxyxanthone ( 6 ). Structure of compound 1 was elucidated with the aid of IR, UV, NMR, and MS data, and chemical transformation via new allyloxy xanthone derivative ( 2 ). Compounds 1 – 6 exhibited various levels of antioxidant and anti‐α‐glucosidase activities. Absorption and fluorescence spectroscopic studies on 1 – 6 indicated that these compounds could interact with calf thymus DNA (CT‐DNA) through intercalation and with bovine serum albumin (BSA) in a static quenching process. Compound 1 was found to be significantly cytotoxic against human cancer cell lines HeLa, HCT116, and AGS, and weakly active against normal NIH 3T3 cell line.     

Cytotoxic ent‐Kaurane Diterpenoids from Isodon nervosus

Four new ent‐kaurane diterpenoids, rabdonervosins G–J ( 1 – 4 , resp.), were isolated from the leaves and stems of Isodon nervosus. Their structures were elucidated by extensive spectroscopic analyses, including 1D‐, 2D‐NMR and HR mass spectra. Compound 2 showed potent cytotoxicity against the HepG2 and PC‐9/ZD cell lines with IC₅₀ values of 2.36 and 6.07 μM , respectively, and compound 3 exhibited cytotoxicity against the HepG2 and CNE2 cell lines with IC₅₀ values of 8.64 and 9.77 μM , respectively.     

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.     

Three new cytochalasins from the marine-derived fungus Spicaria elegans KLA03 by supplementing the cultures with L- and D-tryptophan

Three new cytochalasins Z₂₁–Z₂₃ ( 1 – 3 , resp.), together with five analogs, 4 – 8 , were isolated from Spicaria elegans KLA03 by the OSMAC (one strain‐many compounds) approach with adding L ‐ and D ‐tryptophan during its cultivation. The structures of new cytochalasins were elucidated on the basis of comprehensive 1D‐ and 2D‐NMR and HR‐ESI‐MS analyses. Cytochalasins Z₂₁ and Z₂₂ ( 1 and 2 , resp.), and compound 5 showed cytotoxic activities against A‐549 cell lines with IC₅₀ values of 8.2, 20.0, and 3.1 μM , respectively.     

Two New Anti‐Proliferative C18‐Norditerpenes from the Roots of Podocarpus macrophyllus

Activity‐guided fractionation strategy was used to investigate chemical constituents from the roots of Podocarpus macrophyllus. Successfully, two new norditerpenes, 2β‐hydroxymakilactone A ( 1 ) and 3β‐hydroxymakilactone A ( 2 ), along with ten known analogues ( 3  –  12 ) were isolated. The structures of 1 and 2 were elucidated by spectroscopic analysis including 1D‐, 2D‐NMR, and HR‐ESI‐MS data. The previously reported structure of 2,3‐dihydro‐2α‐hydroxypodolide was revised as 2,3‐dihydro‐2β‐hydroxypodolide ( 3 ) by spectroscopic analysis, and was further confirmed by X‐ray crystallographic analysis. Cytotoxic activities of all isolated compounds against five human solid tumour cell lines (AGS, HeLa, MDA‐MB‐231, HepG‐2, and PANC‐1) were evaluated. All of them exhibited anti‐proliferative activities (IC₅₀ = 0.3 – 27 μm ), except for 10 . Compounds 1 , 4 , 5 , 6 , and 8 exhibited potent inhibitory activities with IC₅₀ < 1 μm against HeLa and AGS cells.     

Tirucallane Triterpenoids from the Stems of Brucea mollis

Three new tirucallane triterpenoids, brumollisols A–C ( 1 – 3 , resp.), together with five known analogues, (23R,24S)‐23,24,25‐trihydroxytirucall‐7‐ene‐3,6‐dione ( 4 ), piscidinol A ( 5 ), 24‐epipiscidinol A ( 6 ), 21α‐methylmelianodiol ( 7 ), and 21β‐methylmelianodiol ( 8 ), were isolated from an EtOH extract of the stems of Brucea mollis. Their structures were elucidated by means of spectroscopic methods including 1D‐ and 2D‐NMR techniques and mass spectrometry. In the in vitro assays, compound 6 exhibited significant cytotoxic activity against A549 and BGC‐823 cancer cells with IC₅₀ values of 1.16 and 3.01 μM , respectively. At a concentration of 10 μM , compounds 1 – 5, 7 , and 8 were found to inhibit NO production in mouse peritoneal macrophages with inhibitory ratios ranging from 39.8±7.7 to 68.2±4.5%.     

Synthesis,Molecular Modeling,and Biological Evaluation of Novel Chiral Thiosemicarbazone Derivatives as Potent Anticancer Agents

A series of new chiral thiosemicarbazones derived from homochiral amines in both enantiomeric forms were synthesized and evaluated for their in vitro antiproliferative activity against A549 (human alveolar adenocarcinoma), MCF‐7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), and HGC‐27 (human stomach carcinoma) cell lines. Some of compounds showed inhibitory activities on the growth of cancer cell lines. Especially, compound 17b exhibited the most potent activity (IC₅₀ 4.6 μM) against HGC‐27 as compared with the reference compound, sindaxel (IC₅₀ 10.3 μM), and could be used as a lead compound to search new chiral thiosemicarbazone derivatives as antiproliferative agents. Chirality 27:177–188, 2015. © 2014 Wiley Periodicals, Inc.     

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 .     

Chagosendines A – C,New Metal Complexes of Imidazole Alkaloids from the Calcareous Sponge Leucetta chagosensis

Chemical examination of the bright yellow sponge Leucetta chagosensis resulted in the isolation of three new imidazole‐based alkaloid complexes namely chagosendines A – C ( 1  –  3 ), together with known analogues pyronaamidine, naamidine J, and naamine C. Their structures were determined on the basis of extensive spectroscopic (IR, MS, NMR, and single‐crystal X‐ray diffraction) analysis in association with the chemical conversion. The isolated alkaloids together with three synthesized new homodimer complexes were evaluated for the cytotoxic activities against a panel of tumor cell lines. The copper complexes of imidazole alkaloids 2 and 3 , as found from nature for the first time, exerted selective and remarkable activities against the tumor cell lines K562, HepG2, and HeLa.