Guianolides A and B, new carbon skeletal limonoids from the seeds of Carapa guianensis.

Two novel limonoids, named guianolides A (1) and B (2), were isolated from the seeds of Carapa guianensis AUBLET (Meliaceae). Their structures were established by spectroscopic analyses and X-ray crystallography. Guianolides A (1) and B (2) featured an unprecedented carbon skeleton via the formation of a C-11-C-21 bond.

A study on medicinal plants from Malaysia focused on Acalypha siamensis Oliv. ex Gage. isolation and structure of a new tetraterpene, acalyphaser A.

As a part of our chemical studies on Malaysian medicinal plants, five Malaysian plant species were evaluated by cytotoxicity assays using P388 murine leukemia cells. Since Acalypha siamensis exhibited the strongest growth inhibition, its constituents were studied as the object of search for bioactive materials. A novel tetraterpene, acalyphaser A (1), was isolated in the course of the purification. Its structure was elucidated on the basis of 1D- and 2D-NMR techniques, and mass spectrometry.

Lupane and oleanane triterpenoids from the cones of Liquidamber styraciflua.

A new lupane- (1) and a new oleanane-type (2) triterpenoid, together with a known compound, massagenic acid G, were isolated from the cones of Liquidamber styraciflua. The structures of 1 and 2 were determined as 6beta,30-dihydroxy-3-oxolup-20(29)-en-28-oic acid and 3alpha-hydroxy-11-oxoolean-12-en-28-oic acid, respectively, on the basis of spectroscopic methods and chemical conversion. Compound 1 and several structural analogues were evaluated for cytotoxicity against the P388 (murine lymphocyte leukemia) and the A549 (human lung cancer) cell lines.

Cancer chemopreventive effect of orally administrated lupane-type triterpenoid on ultraviolet light B induced photocarcinogenesis of hairless mouse.

Ultraviolet light is the most common cause of skin cancers in human and several effects of ultraviolet light B (UVB) are thought to contribute to skin photocarcinogenesis. The generation of seven triterpenoids from the cones of Liquidamber styraciflua (Hamamelidaceae were examined for their nitric oxide (NO) scavenging activity as the first screening of an in vivo mouse skin anti-initiating assay. 3beta,25-epoxy-3alpha-hydroxylup-20(29)-en-28-oic acid (1), which showed the strongest inhibitory effect among these compounds, was studied further for its anti-tumor initiating activity on mouse models initiated with ultraviolet-B (UVB) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). Oral administration of the compound 1 during a period before and after the three times of UVB irradiation exhibited a remarkable effect: administration of 0.0025% solution of the compound 1 given orally only to the test group, which started 1 week before and ended 1 week after the irradiation, showed approximately 50% inhibition of tumor incidence and tumor multiplicity in comparison to the control group. Thus, compound 1 could act as a potent anti-tumor initiator in UVB radiation photocarcinogenesis.

Cancer chemopreventive activity of lupane- and oleanane-type triterpenoids from the cones of Liquidamber styraciflua.

In a search for cancer chemopreventive agents from natural sources, four lupane-type and seven oleanane-type triterpenoids, and ten synthetic analogs were screened as potential anti-tumor promoters by using the in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) activation assay. Among them, 25-acetoxy-3alpha-hydroxyolean-12-en-28-oic acid (1) and 3beta,25-epoxy-3alpha-hydroxylup-20(29)-en-28-oic acid (2) were examined for anti-tumor promoting activity in a two-stage carcinogenesis assay on mouse skin with 7,12-dimethylbenz[a]anthracene (DMBA) and TPA as promoter. 25-Acetoxy-3alpha-hydroxyolean-12-en-28-oic acid (1) and 3beta,25-epoxy-3alpha-hydroxylup-20(29)-en-28-oic acid (2) showed moderate inhibitory activities.

A new seco-abietane-type diterpene from the stem bark of Picea glehni.

A new seco-abietane-type diterpenoid, 13S-hydroxy-9-oxo-9,10-seco-abiet-8(14)-en-18,10alpha-olide (1) along with a known lignan compound, pinoresinol (2) was isolated from the stem bark of Picea glehni (Fr. Schm.) Masters. Spectroscopic methods and chemical conversions were used to establish the structure of 1. In order to assess their cancer chemopreventive potential, the inhibition of Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) was examined for compound 1, its synthetic analogue, 9,10-seco-8S,13S-epoxy-abiet-8(14)-en-18,10alpha-olide (la) and 2. The inhibitory effect of la on EBV-EA induction was strong (0, 20.7, 67.1 and 89.2 % inhibition at 1000, 500,100 and 10 mol ratio/TPA). The IC50 of la was 226 mol ratio/32 pmol/TPA.

New cytotoxic oleanane-type triterpenoids from the cones of Liquidamber styraciflua.

Two new oleanane-type triterpenoids (1 and 2), together with two known compounds, 6beta-hydroxy-3-oxo-lup-20(29)-en-28-oic acid (3) and 3,11-dioxoolean-12-en-28-oic acid (4), were isolated from the stem bark of Liquidamber styraciflua. The structures of 1 and 2 were determined to be 25-acetoxy-3alpha-hydroxyolean-12-en-28-oic acid (1) and 3alpha,25-dihydroxyolean-12-en-28-oic acid (2) on the basis of spectroscopic methods and chemical conversion. Compound 1 showed strong cytotoxicity against a disease-oriented panel of 39 human cancer cell lines, although compounds 2, 3, and 4 showed weaker activity compared to 1.

Cancer chemopreventive activity of serratane-type triterpenoids from Picea jezoensis.

To search for cancer chemopreventive agents from natural sources, 13alpha,14alpha-epoxy-21alpha-methoxyserratan-3-one, 21alpha-methoxyserrat-13-en-3-one, and 21alpha-hydroxy-3beta-methoxyserrat-14-en-30-al isolated from the cuticle of Picea jezoensis (Sieb. et Zucc.) Carr. var. jezoensis (Pinaceae) were investigated for inhibitory effects in a two-stage mouse skin carcinogenesis test on mouse skin with 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter. 21Alpha-hydroxy-3beta-methoxyserrat-14-en-30-al and 13alpha,14alpha-epoxy-21alpha-methoxyserratan-3-one were found to exhibit strong antitumor-promoting activities in the in vivo carcinogenesis test.

Cancer chemopreventive activity of serratane-type triterpenoids on two-stage mouse skin carcinogenesis.

Eleven serratane-type triterpenoids isolated from the stem bark of Picea jezoensis (Sieb. et Zucc.) Carr. var. jezoensis (Pinaceae) and the stem bark of Picea jezoensis (Sieb. et Zucc.) Carr. var. hondoensis (Mayer) Rehder (Pinaceae) and three synthetic analogs were studied for their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). 21-Episerratenediol, serratenediol, diepiserratenediol, 3 beta-hydroxyserrat-14-en-21-one, 3 alpha-methoxy-21 beta-hydroxyserrat-14-en-16-one, 3 beta-methoxyserrat-14-en-21 beta-yl acetate, 3 alpha-methoxyserrat-14-en-21 beta-yl acetate and 3 beta-methoxyserrat-14-en-21 alpha-yl acetate demonstrated strong inhibitory effects on the EBV-EA activation without showing any cytotoxicity, their effects being stronger than that of a representative control, oleanolic acid. Furthermore, 21-episerratenediol exhibited a remarkable inhibitory effect on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene as an initiator and TPA as a promoter. The result of the present investigation indicated that 21-episerratenediol might be valuable as a potent cancer chemopreventive agent.

Two new anti-tumor promoting serratane-type triterpenoids from the stem bark of Picea jezoensis var. jezoensis.

Two new serratane-type triterpenoids, 1 and 2, were isolated from the stem bark of Picea jezoensis Carr. var. jezoensis (Pinaceae). Their structures were determined to be 3beta-methoxyserrat-13-en-21beta-ol (1) and 13beta, l4beta-epoxy-3beta-methoxyserratan-21beta-ol (2) on the basis of spectroscopic methods and partial syntheses. Compounds 1 and 2 and their acetates were screened as potential anti-tumor promoters by using the in vitro short-term 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) activation assay. IC50 value evaluation showed that compound 1 was more effective than others. In addition, compounds 1 and 2 were examined for anti-tumor promoting activities in a two-stage carcinogenesis assay of mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Compounds 1 and 2 exhibited significant anti-tumor promoting effects on mouse skin carcinogenesis.

Lack of modification of rat hepatocarcinogenesis by fernane-type triterpenoids, isolated from a Euphorbia genus.

Inhibitors of topoisomerases, enzymes that produce an unusual type of DNA damage, are considered as antitumor agents. Recently it has been reported that the fernane-type triterpenoid EC-2 and its hydroxyl derivative, isolated from Euphorbia, are potent topoisomerase II inhibitors. In this study, the modifying effects of EC-2 and EC-4 on the development of putative preneoplastic lesions, glutathione S-transferase placental form (GST-P)-positive foci, in the liver of rats were investigated using a medium-term bioassay system. Fisher 344 male, 6-week-old rats were given a single intraperitoneal injection (200 mg/kg b.w.) of diethylnitrosamine or saline at the beginning of the experiment and subjected to 2/3 partial hepatectomy at the 3rd week. The test compounds were administered five times/week by i.g. gavage at a dose of 1 mg/kg b.w. from 2 to 8 weeks. Quantitation of the numbers and areas per cm(2) of induced GST-P positive foci did not demonstrated any significant differences among the groups and no variation in cell proliferation as indicated by 5-bromo- 2'-deoxyuridine (BrdU) labeling. Our results suggest that EC-2 and EC-4 have no modifying effects on rat hepatocarcinogenesis.

Tetracyclic triterpenes and other constituents from the leaves and bark of Larix kaempferi.

Two new triterpenes were isolated from the leaves of Larix kaempferi together with two known compounds, 24-methylenecycloartanone and 24-methylenecycloartanol. A new triterpene-triol, nine known compounds, n-alkyl trans-ferulates and trans-p-coumarates, rheosmin, five stigmastanes and friedelin were isolated from the stem bark. These new compounds were characterized as cycloartan-3,24-dione, 24-methylenecycloartan-3alpha-ol and lanost-9(11)-en-3alpha,24S,25-triol on the basis of chemical and spectroscopic evidence.