Dantaxusins A and B, two new taxoids from Taxus yunnanensis.

Two new taxane diterpenes, dantaxusin A [5 alpha-cinnamoyloxy-2 alpha,7 beta,13 alpha-triacetoxy-2(3-->20)abeo-taxa-4(20),11-diene-9,10-dione (1)] and dantaxusin B [5 alpha-cinnamoyloxy-9 alpha-hydroxy-10 beta,13 alpha-diacetoxytaxa-4(20),11-diene (2)], were isolated from an ethanol extract of the aerial parts of Taxus yunnanensis along with taxuspine B, 2-deacetoxytaxinine J, taxuyunnanine C, taxinine B, taxuspine C, and taxinine NN-4. The structures of 1 and 2 were established on the basis of 1D and 2D NMR and HRMS spectroscopic methods.

Cytotoxity of non-alkaloidal taxane diterpenes from Taxus chinensis against a paclitaxel-resistant cell line.

Seven taxane diterpenes were isolated from the EtOH extract of the aerial parts of Taxus chinensis, and evaluated for cytotoxicity against nine human cell lines, including a beta-tublin mutant resistant to paclitaxel. Compound 2, a non-alkaloid-type taxane diterpene, showed significant cytotoxicity in most cell lines, and notably, equipotent against both parental and beta-tublin mutant tumor cell lines.

Conversion of quassinoids for enhancement of inhibitory effect against Epstein-Barr virus early antigen activation. Introduction of lipophilic side chain and esterification of diosphenol.

Introduction of a senecioyl group into shinjulactones B and C, and esterification of the diosphenol moiety in brusatol and brucein A enhanced inhibitory effect against Epstein-Barr virus early antigen activation.

A new taxoid, 19-acetoxytaxagifine, from Taxus chinensis.

A new taxane diterpene, 19-acetoxytaxagifine (1), was isolated from an ethanol extract of the aerial parts of Taxus chinensis. Its structure was determined on the basis of spectral evidence.

Anti-tuberculosis activity of quassinoids.

In vitro evaluation of anti-tuberculosis activity was conducted for fifty-six quassinoids isolated in our laboratory from Simaroubaceous plants, Ailanthus altissima (= Aa, 10 compounds), Brucea antidysenterica (= Ba, 16 compounds), Picrasma ailanthoides (= Pa, 14 compounds), and Brucea javanica (= Bj, 16 compounds). Of the compounds tested, shinjulactone K (1), ailanthone (2), shinjudilactone (3), and dehydrobruceantin (4) were the most potent. Although the activities were very low (0-19%), the resulting data provided a picture of structure-activity relationships.

Synthesis of cytotoxic fluorinated quassinoids.

The C-15 senecioyl side chain of brusatol was interchanged with fluorinated acyl groups, and the C-3 hydroxy group of bruceolide was esterified with fluorinated acyl chlorides. These fluorinated quassinoids 11, 12, 13, and 17 showed significant cytotoxic activity against eight human cancer cell lines including small and non-small cell lung, colon, CNS, ovarian and renal cancers, leukemia, and melanoma with 17 being about 100 times more potent than 11, 12, and 13. The activity of 17 was similar to that of bruceantin (1) in this in vitro cell line panel.

Inhibitory effects of quassinoid derivatives on Epstein-Barr virus early antigen activation.

Short-term in vitro assays for tumor promoters and antitumor promoters (Epstein-Barr virus activation test) were carried out for semisynthetic quassinoids (3-7), which were obtained by esterification of the C-15 OH group of deacetylated isobrucein-B (2). All the ester derivatives showed higher antitumor promoting activity than that of the potent compound 2. A compound containing a fluorinated aliphatic ester showed the highest potency.

Quassinoids as inhibitors of Epstein-Barr virus early antigen activation.

Short-term in vitro assays for tumor promoters and antitumor promoters (Epstein-Barr virus activation test) were carried out for 14 quassinoids isolated from Ailanthus altissima. Some quassinoids, including ailantinol B, ailantinol C, ailanthone, and shinjulactone A, showed moderate activity at a molar ratio of 1:100 (TPA/quassinoids), and the results led to the elucidation of structure-activity relationships.

Bruceanols G and H cytotoxic quassinoids from Brucea antidysenterica.

Two new quassinoids, bruceanols G [1] and H [4], were isolated from Brucea antidysenterica, and their structures were elucidated by spectral evidence and chemical transformation. Bruceanol G exhibited significant cytotoxicity against the COLO-205 and KB neoplastic cell lines with ED50 values of 0.44 and 0.55 microM, respectively.

Inhibitory effects of quassinoids on Epstein-Barr virus activation.

Short-term in vitro assays for tumor promoters and anti-tumor promoters (Epstein-Barr virus activation test) were carried out for 45 quassinoids. As a result, some quassinoids showed potent activity, more than 50% inhibition at a molar ratio of 1:1 (TPA/quassinoids). These results led to the following structure-activity relationships: (1) a methyleneoxy bridge and side chain enhance the activity and (2) a sugar moiety reduces the activity.

Bruceosides D, E, and F, three new cytotoxic quassinoid glucosides from Brucea javanica.

Three new quassinoid glucosides, bruceosides D [1], E [2], and F [3], were isolated from Brucea javanica, and their structures were elucidated by spectral evidence and chemical transformation to known compounds. Compounds 1-3 show selective cytotoxicity in the leukemia and non-small cell lung, colon, CNS, melanoma, and ovarian cancer cell lines with log GI50 values in the range of -4.14 to -5.72.

Bruceanols D, E, and F three new cytotoxic quassinoids from Brucea antidysenterica.

Three new quassinoids, bruceanols D [1], E [2], and F [3], were isolated from Brucea antidysenterica, and their structures were elucidated by spectral evidence and chemical transformation. All of these compounds exhibited cytotoxicity against five human tumor cell lines, malignant melanoma (RPMI-7951), lung carcinoma (A-549), ileocecal adenocarcinoma (HCT-8), epidermoid carcinoma of the nasopharynx (KB), and medulloblastoma (TE-671), and against murine lymphocytic leukemia (P-388).

Antifeedant and Insecticidal Activity of Quassinoids against Diamondback Moth (Plutella xylostella).

The antifeedant and insecticidal activities of sixteen quassinoids against 3rd instar larvae of the diamondback moth (Plutella xylostella) were compared with those of known insect antifeedant chlordimeform (1), and the structure-activity relationship was discussed. The insecticidal activity of quassin (2) was higher than that of 1, although its antifeedant activity was nearly the same as that of the reference compound.

Antitumor agents, 127. Bruceoside C, a new cytotoxic quassinoid glucoside, and related compounds from Brucea javanica.

Bruceoside C [5], a new quassinoid glucoside, and related compounds were isolated from Brucea javanica, and their structures were elucidated by spectral data. Bruceoside C showed potent cytotoxicities against KB, A-549, RPMI, and TE-671 tumor cells.

Picrasinoside H, a new quassinoid glucoside, and related compounds from the stem wood of Picrasma ailanthoides.

A new quassinoid glucoside, picrasinoside H [1], and five known quassinoids have been isolated from the stem wood of Picrasma ailanthoides. The structures of these quassinoids were elucidated on the basis of spectral evidence.

Antitumor agents, 118. The isolation and characterization of bruceanic acid A, its methyl ester, and the new bruceanic acids B, C, and D, from Brucea antidysenterica.

The known bruceanic acid A [1] and its methyl ester 2, as well as the new bruceanic acids B [3], C [4], and D [5], have been isolated from Brucea antidysenterica. The structures of 1-5 were elucidated by spectral data. Compound 1 demonstrated cytotoxicity against KB and TE671 tumor cells. Compound 5 was cytotoxic against P-388 lymphocytic leukemia cells.

Antitumor agents, 104. Isolation of yadanziosides M and P from Brucea antidysenterica and identification of bruceantinoside B as a mixture of yadanzioside P and bruceantinoside C.

Yadanziosides M [3] and P [1] were isolated from Brucea antidysenterica. Their structures were elucidated by spectral data. Bruceantinoside B reported previously was reinvestigated and revealed to be a mixture of yadanzioside P and bruceantinoside C [2]. The structure of yadanzioside P was found to be identical to that of bruceantinoside B.

Antitumor agents, 90. Bruceantinoside C, a new cytotoxic quassinoid glycoside from Brucea antidysenterica.

Three cytotoxic, quassinoid glycosides, the new bruceantinoside C [1] and the known yadanziosides G [2] and N [3] were isolated from the stem of Brucea antidysenterica. The structures of 1-3 were determined from their spectral data.