Niphatoxin C, a cytotoxic tripyridine alkaloid from Callyspongia sp

As part of our studies to discover P2X 7 receptor antagonists, the sponge Callyspongia sp. was investigated. A new tripyridine alkaloid niphatoxin C ( 1) was isolated and had P2X 7 receptor antagonism; however, cytotoxicity of THP-1 cells was the predominant biological effect at higher concentrations. Its structure was determined by 1- and 2-D NMR spectroscopy.     

Renieramycin J,a highly cytotoxic tetrahydroisoquinoline alkaloid,from a marine sponge Neopetrosia sp.

Renieramycin J (1), a new tetrahydroisoquinoline alkaloid, has been isolated from a marine sponge Neopetrosia sp. as a potent cytotoxin that induced morphological changes in 3Y1 cells. Such changes are characteristic of RNA and/or protein synthesis inhibitors. The structure of 1 including the absolute stereochemistry was determined by spectroscopic and chemical methods.     

Coproverdine,a novel,cytotoxic marine alkaloid from a new zealand ascidian

The crude extract of a New Zealand ascidian displayed antitumor activity. Bioassay-directed fractionation yielded a novel alkaloid, coproverdine (1). The structure of 1 was assigned on the basis of detailed spectroscopic analysis. Coproverdine (1) was responsible for the antitumor activity of the crude extract.     

Antineoplastic agents 440. Asymmetric synthesis and evaluation of the combretastatin A-1 SAR probes (1S,2S)- and (1R,2R)-1, 2-dihydroxy- 1-(2',3'-dihydroxy-4'-methoxyphenyl)-2-(3' ',4' ',5' '-trimethoxyphenyl)-ethane

The synthetic (E)-isomer (3b) of natural combretastatin A-1 (1a) isolated from the African bushwillow Combretum caffrum was the focus of chiral hydroxylation (Sharpless) reactions as part of a structure-activity relationship study. The resulting (R,R)- and (S,S, )-diols (6 and 7) and synthetic intermediates were evaluated against a series of cancer cell lines, microorganisms, and tubulin. Chiral diols 6 and 7 showed increased activity against the P-388 murine lymphocytic leukemia cell line with ED(50) values of 3.9 and 2.9 microg/mL, respectively, when compared to the precursor (E)-stilbene 3b. In contrast, (E)-stilbene 3b exhibited more potent antibiotic activity than the chiral diols (6 and 7). Both diols, (R,R)-6 and (S, S)-7, displayed less cancer cell growth inhibition and less antibiotic activity than did natural combretastatin A-1 (1a) (P-388 ED(50) 0.25 microg/mL).     

Antitumor agents, 112. Emarginatine B, a novel potent cytotoxic sesquiterpene pyridine alkaloid from Maytenus emarginata

A new sesquiterpene pyridine alkaloid, emarginatine B [2] has been isolated, along with maytansine [3], from Maytenus emarginata. Emarginatine B showed potent cytotoxicity against human KB cells (ED50 = 0.4 micrograms/ml). Spectral correlations established its structure as a 9-benzoate and C-8 epimer of emarginatine A [1]. The conformational aspect of the latter compound was elucidated by nmr studies, including the use of 2D-nmr techniques and difference nOe methods.     

Inhibition of cyclo-oxygenase-2 expression in mouse macrophages by 4-(3-methyl-but-1-enyl)-3,5,3',4'-tetrahydroxystilbene, a resveratrol derivative from peanuts

Resveratrol derivatives are of interest as inhibitors of cyclo-oxygenase-2 and as antiinflammatory agents. The prenylated resveratrol derivative 4-(3-methyl-but-1-enyl)-3,5,3',4'-tetrahydroxystilbene was purified from fungally infected peanuts by thin layer chromatography and its structure was confirmed by mass spectrometry. 4-(3-Methyl-but-1-enyl)-3,5,3',4'-tetrahydroxystilbene inhibited lipopolysaccharide-induced expression of cyclo-oxygenase-2 protein and cyclo-oxygenase-2 mRNA in mouse macrophages at concentrations that were non-cytotoxic. 4-(3-Methyl-but-1-enyl)-3,5,3',4'-tetrahydroxystilbene warrants further evaluation as an antiinflammatory agent.     

11-oxoaerothionin: a cytotoxic antitumor bromotyrosine-derived alkaloid from the Caribbean marine sponge Aplysina lacunosa.

A new cytotoxic bromotyrosine-derived secondary metabolite, 11-oxoaerothionin [3], was isolated from the Caribbean sea sponge Aplysina lacunosa. The structure of 3 was argued on the basis of detailed spectroscopic analysis and by chemical conversion to the known antibiotic compound 11-hydroxyaerothionin [2]. When screened against a panel of four human cell lines, 11-oxoaerothionin [3] showed pronounced as well as selective antitumor activity toward the human colon (HCT 116) cell line within the limited concentration range of 0.01-0.1 microgram/ml.     

Two new natural azafluorene alkaloids and a cytotoxic aporphine alkaloid from Polyalthia longifolia

The stem and stem bark of Polyalthia longifolia afforded the cytotoxic aporphine alkaloid liriodenine [1], as well as two aporphine alkaloids, noroliveroline [2] and oliveroline-beta-N-oxide [3] and three azafluorene alkaloids, darienine [4], polyfothine [6], and isooncodine [7], which are not bioactive. Polyfothine [6] and isooncodine [7] are new natural compounds.     

Antitumor agents, 130, Novel 4 beta-arylamino derivatives of 3',4'-didemethoxy-3',4'-dioxo-4-deoxypodophyllotoxin as potent inhibitors of human DNA topoisomerase II.

A series of ortho-quinone analogues 1-28 of podophyllotoxin possessing various C-4 beta-aniline moieties have been synthesized and evaluated for their inhibitory activity against human DNA topoisomerase II, their activity in causing cellular protein-linked DNA breakage, and their cytotoxicity against KB cells. Compounds 8-12, 15, 19, and 23-28 are better than or comparable to etoposide in their inhibition of the human DNA topoisomerase II, while compounds 8-10 and 22 are comparable to or more potent than etoposide in causing DNA breakage. There is an apparent lack of correlation between cytotoxicity and the ability of these compounds to cause protein-linked DNA breaks or inhibit DNA topoisomerase II. This suggests that in addition to the mechanism of the topoisomerase II involving DNA breakages, other mechanisms of action, such as the radical mechanism or the direct adduct formation of the ortho-quinone with DNA or protein, may also involve and account for the apparent KB cytotoxicity. Two different modes of DNA topoisomerase II inhibition for 8-28 were proposed.     

Acetylanonamine, a new secopyrrolizidine alkaloid from Senecio anonymus.

A new secopyrrolizidine alkaloid, acetylanonamine, was isolated from Senecio anonymus. The structure was established by high resolution nmr (1H-1H COSY and 1H-13C HETCOR), ms, comparison of these spectral data with those of anonamine, and synthesis of 1 from 2.     

Myriaporones 1-4, cytotoxic metabolites from the Mediterranean bryozoan Myriapora truncata

Four novel polyketide-derived metabolites, myriaporones 1, 2, 3, and 4, have been isolated from the Mediterranean bryozoan Myriapora truncata. Their structures and stereochemistry have been assigned from the analysis of spectroscopic data. The inseparable equilibrium mixture of myriaporones 3 and 4 showed 88% inhibition of L1210 murine leukemia cells at 0.2 microg/mL.     

八角枫根中1个新的生物碱及其细胞毒活性研究

对八角枫Alangium chinense根的化学成分进行研究,运用硅胶、凝胶、MCI-gel树脂及RP-HPLC等多种色谱技术分离纯化,并根据理化性质和波谱数据鉴定化合物的结构,同时用MTT法测定化合物的细胞毒活性。从八角枫根的90%乙醇提取物中分离鉴定了3个生物碱类化合物(1~3),其中化合物1为新化合物,命名为8-羟基-3-羟甲基-6,9-二甲基-7H-苯并[de]异喹啉-7-酮,其对NB4,A-549,SHSY5Y,PC-3,MCF-7的IC50分别为4.2,3.5,5.7,2.8,3.9μmol·L-1,该化合物具一定的细胞毒活性。     

Structural characterization and cytotoxic properties of a 4-O-methylglucuronoxylan from castanea sativa. 2. Evidence of a structure-activity relationship

Xylans were purified from delignified holocellulose alkaline extracts of Castanea sativa (Spanish chestnut) and Argania spinosa (Argan tree) and their structures analyzed by means of GC of their per-trimethylsilylated methylglycoside derivatives and (1)H NMR spectroscopy. The structures deduced were characteristic of a 4-O-methylglucuronoxylan (MGX) and a homoxylan (HX), respectively, with degrees of polymerization ranging from 182 to 360. In the case of MGX, the regular or random distribution of 4-O-methylglucuronic acid along the xylosyl backbone--determined by MALDI mass spectrometry after autohydrolysis of the polysaccharide--varied and depended both on the botanical source from which they were extracted and on the xylan extraction procedure. The MGX also inhibited in different ways the proliferation as well as the migration and invasion capability of A431 human epidermoid carcinoma cells. These biological properties could be correlated with structural features including values of the degree of polymerization, 4-O-MeGlcA to xylose ratios, and distribution of 4-O-MeGlcA along the xylosyl backbone, giving evidence of a defined structure-activity relationship.     

Phytotoxins from Hofmeisteria schaffneri: isolation and synthesis of 2'-(2' '-hydroxy-4' '-methylphenyl)-2'-oxoethyl acetate1

Activity-directed fractionation of a CH(2)Cl(2)-MeOH (1:1) extract of Hofmeisteria schaffneri led to the isolation of a new phytotoxin characterized as 2'-(2' '-hydroxy-4' '-methylphenyl)-2'-oxoethyl acetate and designated the trivial name of hofmeisterin (1). In addition, the known compounds beta-carotene, euparin, and 3',4',4a',9a'-tetrahydro-6,7'-dimethylspiro[benzofuran-3(2H),2'-pyrano[2,3-b]benzofuran]-2,4a'-diol (2) were obtained. The identification of the isolates was accomplished by spectroscopic methods. The structure of 1 was unequivocally confirmed by synthesis. The methyl derivative 1a was also synthesized following the same strategy. Compounds 1 and 2 inhibited radicle growth of Amaranthus hypochondriacus (IC(50) = 3.2 x 10(-4) and 1.2 x 10(-5) M, respectively) and significantly inhibited activation of the calmodulin (CaM)-dependent enzyme cAMP phosphodiesterase (PDE) with IC(50) values of 4.4 and 4.22 microM, respectively.     

Thalibealine, a novel tetrahydroprotoberberine--aporphine dimeric alkaloid from Thalictrum wangii.

A novel tetrahydroprotoberberine-aporphine dimeric alkaloid, (-)-thalibealine (1), was isolated from the roots of Thalictrum wangiii, and its structure established via spectroscopic analysis. Three other alkaloids were isolated, including the benzyltetrahydroisoquinoline-aporphine dimer (+)-thalmelatidine, the aporphine (+)-magnoflorine, and the protoberberine berberine. This is the first reported isolation of a tetrahydroprotoberberine-aporphine dimer from nature, as well as the first reported isolation of constituents from Thalictrum wangii.     

Isolation, structure elucidation, and biological evaluation of 15-amido-3-demethoxy-2alpha,3alpha-methylenedioxyerythroculine, a new alkaloid from Hyperbaena valida

A phytochemical investigation of the leaves of Hyperbaena valida resulted in the isolation and characterization of two erythrina-type alkaloids, 1 and 2, which were found to be antagonists at nicotinic receptors. Compound 1 was assigned as the new 15-amido-3-demethoxy-2alpha,3alpha-methylenedioxyerythroculine and compound 2 as the known 3-demethoxy-2alpha,3alpha-methylenedioxyerythroculine. Antagonism of a 100 microM nicotine response was observed for alkaloid 1 (IC50 value of 94 +/- 8 microM) and alkaloid 2 (IC50 value of 77 +/- 19 microM).     

Kulokekahilide-2, a cytotoxic depsipeptide from a cephalaspidean mollusk Philinopsis speciosa

A cytotoxic depsipeptide, kulokekahilide-2 (1), was isolated from a cephalaspidean mollusk, Philinopsis speciosa. The structure elucidation of kulokekahilide-2 was carried out by spectroscopic analysis and chemical degradation. Kulokekahilide-2 showed potent cytotoxicity against several cell lines (P388, SK-OV-3, MDA-MB-435, and A-10 with IC50 values ranging from 4.2 to 59.1 nM) indicating cancer cell selectivity.