Artoindonesianin L, a new prenylated flavone with cytotoxic activity from Artocarpus rotunda.

A new prenylated flavone, named artoindonesianin L (1), was isolated from Artocarpus rotunda (Hout) Panzer (Moraceae). Its structure was elucidated as on the basis of spectroscopic evidence. Along with this new compound, four known phenolic compounds were also isolated from this plant and identified as artonins M (2) and E (3), cycloartobiloxanthone (4) and artonin O (5). All these compounds showed significant cytotoxicity against murine P388 leukemia cells.

Celogentins A-C, new antimitotic bicyclic peptides from the seeds of Celosia argentea.

Three new bicyclic peptides, celogentins A (1), B (2), and C (3), have been isolated together with a known-related peptide, moroidin (4), from the seeds of Celosia argentea, and their structures including absolute stereochemistry were determined by using extensive NMR methods and chemical means. Celogentins A (1), B (2), and C (3) inhibited the polymerization of tubulin, and celogentin C (3) was four times more potent than moroidin (4) in the inhibitory activity. Structure-activity relationship study using moroidin derivatives 5-7 and analogue 8 as well as celogentins A-C (1-3) and moroidin (4) indicates that the bicyclic ring system including unusual non-peptide connections among beta(s)-Leu, Trp, and His residues characteristic of celogentins and moroidin, with ring size and conformations suitable for interaction with tubulin would be important for their biological activity.

The cytotoxicity and chemical constituents of the hexane fraction of Typhonium flagelliforme (Araceace).

The plant, Typhonium flagelliforme (Araceae), commonly known as the "rodent tuber" in Malaysia, is often used as an essential ingredient of herbal remedies for alternative cancer therapies. The hexane extract of this plant was evaluated for cytotoxic activity against in vitro culture on P388 murine leukaemia cells and showed weak IC(50) of 15 microg/ml. The partial chemical constituents were identified as methyl esters of hexadecanoic acid, octadecanoic acid, 9-octadecenoic acid and 9,12-octadecadienoic acid. In addition, several common aliphatics were identified as dodecane, tridecane, tetradecane, pentadecane, hexadecane, heptadecane, octadecane, nonadecane and eicosane. The unique methyl ester of 13-phenyltridecanoic acid was isolated and positively identified using spectroscopic methods. None of the identified compounds showed or are known to have cytotoxic behaviour.

Cytotoxic activity of Typhonium flagelliforme (Araceae).

The plant Typhonium flagelliforme (Araceae), commonly known as the 'rodent tuber', is often included as an essential ingredient in various herbal remedies recommended for cancer therapies in Malaysia. Various extracts prepared from either the roots, tubers, stems or leaves were tested for cytotoxic activity on murine P388 leukaemia cells using the MTT assay method. Both the chloroform (IC50 = 6.0 microg/mL) and hexane (IC50 = 15.0 microg/mL) extract from the 'roots and tubers' exhibited weak cytotoxic activity. The hexane extract (IC50 = 65.0 microg/mL) from the 'stems and leaves' exhibited weaker cytotoxic activity than the chloroform extract (IC50 = 8.0 microg/mL). Although the juice extract from the 'roots and tubers' is frequently consumed for cancer treatment, it exhibited poor cytotoxic activity. Further analysis using an amino acid analyser revealed that the juice extract contained a high concentration of arginine (0.874%). A high tryptophan content (0.800%) was confirmed by NMR and HPLC analysis.

Cedronolactone E, a novel C(19) quassinoid from Simaba cedron.

A novel pentacyclic C(19) quassinoid, cedronolactone E (1), was isolated from the wood of Simaba cedron. Its structure was elucidated by interpretation of spectroscopic data.

Further quinoidal derivatives from Rubia cordifolia L.

Two new quinoidal dimers, a new naphthohydroquinone anhydride, a known naphthoic acid ester derivative and two known benzoic acid derivatives were isolated from the chloroform fraction of a chloroform-methanol (1:1) extract of Rubia cordifolia L. The identification of these compounds was based on spectral analysis.

[Antitumor compounds isolated from higher plants].

A lot of anticancer agents have been isolated from natural sources, especially from microorganisms and plants. However, there is no special type of compounds for cancer therapy. Various types of substances are effective for various types of cancers and tumors: for instance, alkaloids, lignans, terpenes and steroids, etc. In this report, the authors will describe especially about higher plants.

Structure-activity relationship of cardiotonic flavonoids in guinea-pig papillary muscle.

Sixteen flavonoids were tested for a positive inotropic effect (PIE) on guinea-pig papillary muscle paced at 0.2 Hz in a Krebs-Henseleit solution at 30 degrees C. The structure-activity relationship was investigated by determining both the pD2 value and the intrinsic activity in the case of ten flavonols, three flavones, one flavanone and two catechins. Quercetin showed the most potent intrinsic activity, and produced the strongest inotropic responses among the 16 compounds. The relative order of potency of the tested flavonoids was quercetin > morin = kaempferol = HEPTA > luteolin = apigenin > natsudaidain = fisetin = galangin. Those that did not produce any PIE were 3-hydroxyflavone, flavone, glycosides of quercetin (rutin and hyperin), flavanones (naringenin) and catechins. With respect to the essential flavonoid nucleus for PIE development, the presence of a hydroxy group at C-4', an alpha, beta-unsaturated ketone on the C-ring and a reasonable lipophilic moiety in the molecule are required. Pharmacological analyses suggest that there is a common mechanism for the PIE and it is cyclic AMP dependent.

Cytotoxic quassinoids from Simaba cedron.

Four new quassinoids, cedronolactones A-D (1-4), together with nine known compounds, simalikalactone D (5), chaparrinone (6), chaparrin (7), glaucarubolone (8), glaucarubol (9), samaderine Z (10), guanepolide (11), ailanquassin A (12), and polyandrol (13), were isolated from the wood of Simaba cedron. The chemical structures of 1-4 were elucidated on the basis of their chemical and spectral properties. Cedronolactone A (1) was shown to exhibit a significant in vitro cytotoxicity (IC50 0.0074 microg/mL) against P-388 cells.

Triterpenoid saponin from Vaccaria segetalis.

A new triterpenoid saponin, vaccaroid B, has been isolated from the seeds of Vaccaria segetalis and its structure was elucidated to be 3beta-hydroxyolean-12-en-23, 28-dioic acid-28-O-beta-D-glucopyranosyl-(1-->3)- beta-D-glucopyranosyl-(1-->6)-[6- O-(3-hydroxy-3-methylglutaryl)-beta-D-glucopyranosyl-(1-->2)]- beta-D-glucopyranoside by spectroscopic methods.

Four new taxoids from Taxus cuspidata var. nana.

Four new taxoids ( 1- 4), showing cytotoxic activity, have been isolated from the stems of Taxus cuspidata Sieb. et. Zucc. var. nana Rehder. Their structures were elucidated by extensive 2D NMR methods including (1)H- (1)H COSY, TOCSY, HMBC, HMQC, and phase sensitive ROESY spectra.

Cyclic octapeptides from Stellaria dichotoma var. lanceolata.

Two new cyclic octapeptides, dichotomin H, cyclo(-Ala-Pro-Thr-Phe-Tyr-P ro-Leu-Ile-), and dichotomin I, cyclo(-Val-Pro-Thr-Phe-Tyr-Pro-Leu-Ile-) have been isolated from the roots of Stellaria dichotoma L. var lanceolata Bge., and their structures were elucidated by extensive two-dimensional NMR methods and chemical degradation.

Taxuspinananes A and B, new taxoids from Taxus cuspidata var. nana.

New taxoids, taxuspinanane A (1), showing potent cytotoxic activity, and taxuspinanane B (2), have been isolated from the stems of Taxus cuspidata Sieb. et. Zucc. var. nana Rehder. Their structures were elucidated by extensive 2D NMR and MS spectroscopic analysis.

Studies on cardiac ingredients of plants. XIII: Chemical modification of gitoxin to cardiotonic compounds without vascular effect.

Nitrated gitoxins (4) and bufotoxin homologues with various lengths of alkyl chain at C-3 of the steroid nucleus (10) were prepared from gitoxin (1). The pharmacological activities of the resulting compounds (4 and 10) were evaluated by measurement of inhibitory effect on NA+, K(+)-adenosine triphosphatase (ATPase) prepared from dog kidney, positive inotropic effect (PIE) on isolated guinea-pig papillary muscle preparations, and the effect on smooth muscle using the mesenteric artery from spontaneously hypertensive rats. Most of the compounds showed a smaller contractile effect on the arterial muscle. Among these compounds, gitoxin 3"-nitrate (4g) exhibited the most desirable biological activities, such as PIE comparable to that of 1, 1.25 times wider concentration-dependent range than 1, and lack of contractile activity on vascular muscle.

Cytotoxic triterpenes from Cleome africana.

Eighteen dammarane-type triterpenes were obtained from the whole plant of Cleome africana by means of cytotoxic bioassay-directed fractionation. Twelve of them were novel compounds whose structures were elucidated by various spectroscopic methods.

Macrocarpals H, I, and J from the Leaves of Eucalyptus globulus.

A 50% EtOH extract of Eucalyptus globulus leaves yielded eight phloroglucinol--sesquiterpene-coupled constituents, including three novel compounds named macrocarpals, H, I, and J. Some of these compounds possessed antibacterial activity against oral pathogenic microorganisms with MIC values ranging from 0.20 micrograms/mL to 6.25 micrograms/mL. Inhibition of glucosyltransferase activity by these compounds was also noted.

Anthraquinones from the polar fractions of Galium sinaicum.

The new anthraquinones, 6,7-dimethoxy xanthopurpurin, 6-hydroxy-7-methoxy rubiadin, 5-hydroxy-6-hydroxymethyl anthragallol 1, 3-dimethyl ether, 7-carboxy anthragallol 1,3-dimethyl ether, anthragallol 1-methyl ether 3-O-beta-D-glucopyranoside, anthragallol 1-methyl ether 3-O-rutinoside, anthragallol 3-O-rutinoside and alizarin 1-methyl ether 2-O-primeveroside were isolated from the CH2Cl2 and n-BuOH extracts of Galium sinaicum roots and their structures were established by various spectroscopic techniques. In addition, two known anthraquinones were also isolated and fully characterized.

Cytotoxic azadirachtin-type limonoids from Melia azedarach.

Four new limonoids, 1-tigloyl-3,20-diacetyl-11-methoxymeliacarpinin, 3-tigloyl-1,20-diacetyl-11-methoxymeliacarpinin, 1-cinnamoyl-3-hydroxy-11-methoxymeliacarpinin, and 1-deoxy-3-methacrylyl-11-methoxymeliacarpinin, together with a known limonoid, 1-cinnamoyl-3-acetyl-11-methoxymeliacarpinin, were isolated from the extract of the root bark of Melia azedarach. The structures were elucidated by spectroscopy.

A cyclic heptapeptide from Vaccaria segetalis.

A new cyclic heptapeptide, segetalin E, cyclo(-Gly-Tyr-Val-Pro-Leu-Trp-Pro-), has been isolated from the seeds of Vaccaria segetalis and the structure elucidated by extensive two-dimensional NMR methods and chemical degradation.

Cyclic peptides from higher plants. 24.1 yunnanin C, a novel cyclic heptapeptide from Stellaria yunnanensis.

A novel cytotoxic cyclic heptapeptide, yunnanin C (1), was isolated from the roots of Stellaria yunnanensis. The structure of 1, cyclo(-Gly-Ile-Gly-Phe-Tyr-Ser-Pro-), was elucidated from spectroscopic evidence and by chemical degradation.