Cytotoxic activity of Brazilian Cerrado plants used in traditional medicine against cancer cell lines.

UNLABELLED: The search for new anti-cancer drugs is one of the most prominent research areas of natural products. Numerous active compounds isolated from Brazilian Cerrado plant species have been studied with promising results. AIM OF THE STUDY: To investigate the cytotoxic potential of 412 extracts from Brazilian Cerrado plants used in traditional medicine belonging to 21 families against tumor cell lines in culture. MATERIAL AND METHOD: Maceration of 50 plant species resulted in 412 hexane, dichloromethane, ethanol and hydroalcohol extracts. The cytotoxicity of the extracts was tested against human colon carcinoma (HCT-8), melanoma (MDA-MB-435), and brain (SF-295) tumor cell lines, using the thiazolyl blue test (MTT) assay. Bioassay-guided fractionation was performed for one active extract. RESULTS AND CONCLUSIONS: Twenty-eight of the 412 tested extracts demonstrated a substantial antiproliferative effect, at least 85% inhibition of cell proliferation at 50 microg/mL against one or more cell lines. Those extracts are obtained from different parts of Anacardiaceae, Annonaceae, Apocynaceae, Clusiaceae, Flacourtiaceae, Sapindaceae, Sapotaceae, Simaroubaceae and Zingiberaceae. Complete dose-response curves were generated and IC(50) values were calculated for these active extracts against four cell lines HCT-8, MDA-MB-435, SF-295 and HL-60 (leukemia), and their direct cytotoxic effects were determined. In summary, 14 extracts of 13 species showed toxicity in all tested tumor cell lines, with IC(50) values ranging from 0.1 to 19.1 microg/mL. The strongest cytotoxic activity was found for the hexane extract of Casearia sylvestris var. lingua stem bark, with an IC(50) of 0.1 microg/mL for HCT-8, 0.9 microg/mL for SF-295, 1.2 microg/mL for MDA-MB-435, and 1.3 microg/mL for HL-60, and Simarouba versicolor root bark, with an IC(50) of 0.5 microg/mL for HCT-8, 0.7 microg/mL for SF-295, 1.5 microg/mL for MDA-MB-435, 1.1 microg/mL for HL-60. Bioassay-guided fractionation of the last extract led to the isolation of glaucarubinone, which showed pronounced activity against the four cell lines studied. Further studies of the active extracts are necessary for chemical characterization of the active compounds and more extensive biological evaluations.

Antiviral activity of simalikalactone D, a quassinoid from Quassia africana.

After removing lipophilic material, the ground root bark of Quassia africana Baill. (Simaroubaceae) was extracted with ethanol 95 %. Partitioning between chloroform, ethyl acetate and water yielded three crude extracts. Pronounced activities were shown by the chloroform and ethyl acetate crude extracts against Herpes simplex, Semliki forest, Coxsackie and Vesicular stomatitis viruses. By repeated column chromatography and preparative thin layer chromatography on silica gel, two quassinoids, i. e., quassin and simalikalactone D were isolated. Structures of the pure compounds were established primarily using NMR spectroscopy. Mass spectral information confirmed the assigned structures. Simalikalactone D was responsible, at least in part, for the high antiviral activity observed for the chloroform crude extract. Quassin showed no activity. For quassinoids the ester group at C-15 and the epoxymethano bridge between C-8 and C-13 appeared to be important structural features in order to exhibit a pronounced antiviral activity.

Quassinoids from the twigs and thorns of Castela polyandra.

The structures of six new C20 quassinoids and one new C19 quassinoid, all isolated from the twigs and thorns of Castela polyandra, were established by a combination of spectroscopic and single-crystal X-ray analysis. Five known quassinoids and one known sterol were also identified.

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.

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).

A new antimalarial quassinoid from Simaba guianensis.

Two antimalarial quassinoids, gutolactone [1] and simalikalactone D [2], have been characterized by bioactivity-directed fractionation from the bark of Simaba guianensis collected near Manaus, Brazil. Compound 2 was previously isolated from Simaba multiflora and Quassia africana and shown to be an active antimalarial in vitro. This is the first occurrence of 1. The structure of the novel quassinoid was established by spectral methods including 2D nmr spectroscopy.

Cytotoxic quassinoids from Cedronia granatensis.

The NCI in vitro primary disease-oriented antitumor screen has been used to select and guide the fractionation of the organic and aqueous extracts of Cedronia granatensis. Two quassinoids, sergiolide [1] and isobrucein B [2], to which the screening panel cell lines exhibited up to a 1000-fold range of differential sensitivity, were isolated. At concentrations of 10(-5)-10(-8) M, the compounds typically produced LC50-level responses against a majority of the melanoma lines and several of the colon, lung, and other solid tumor lines. These and related quassinoids may, therefore, be of interest for in vivo evaluation in appropriate xenograft tumor models.

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.

[Studies on pharmacologically active principles from Indonesian crude drugs. III. Toxic components from Brucea javanica (L.) Merr].

During our screening of pharmacologically active principles from Indonesian medicinal plants by a hypothermic effect the methanol-extract of Brucea javanica (L.) Merr. has been found to exhibit a lethal toxicity to mice. The toxic components were isolated and identified with bruceoside A and B and yadanzioside F. Correction of 13C-nuclear magnetic resonance assignment was also mentioned.

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.

[Studies on the chemical constituents of Brucea javanica (L.) Merr].

An alkaloid and a quassinoid were isolated from the fruit of Brucea javanica (L.) Merr, and were identified as 4-ethoxycarbonyl-2-quinolone (1) and bruceine I (2). Compound 1 was found from natural resource for the first time. The structure of the new compound 2 was elucidated on the basis of spectral data and chemical evidence. Three well known compounds vanillic acid (3), quercetin-3-O-beta-D-galactoside (4), and luteolin-7-O-beta-D-glucoside (5) were also isolated. All of them were first reported to occur in the Brucea genus.

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.

Plants as sources of antimalarial drugs, Part 4: Activity of Brucea javanica fruits against chloroquine-resistant Plasmodium falciparum in vitro and against Plasmodium berghei in vivo.

Extracts of Brucea javanica fruit have been prepared and monitored for their in vitro and in vivo antiplasmodial activities. The antimalarial activity of the fruit was found to be attributable to its quassinoid constituents. Nine of the quassinoids possessed in vitro IC50 values between 0.046-0.0008 microgram/ml against the chloroquine resistant Plasmodium falciparum strain (Kl) tested. The two quassinoid glycosides tested were considerably less active in vitro than the aglycones. Four quassinoids were found to possess activity in vivo against Plasmodium berghei infections in mice after oral dosing. All five quassinoids tested in vivo showed some toxicity.

Plants as sources of antimalarial drugs: in vitro antimalarial activities of some quassinoids.

Fourteen quassinoids, obtained from simaroubaceous plants, were tested for in vitro antimalarial activity. All of these inhibited the incorporation of [3H]hypoxanthine into Plasmodium falciparum in vitro at concentrations below 0.41 microgram ml-1. The two most potent quassinoids, bruceantin and simalikalactone D, showed 50% inhibitory concentration values of 0.0008 and 0.0009 microgram ml-1, respectively. The results are compared with the antiamoebic, antileukemic, and cytotoxic activities of these compounds reported in the literature.

Two new quassinoids from Simaba multiflora fruits.

Two new quassinoids, 13, 18-dehydro-6 alpha-senecioyloxychaparrin (4) and 12-dehydro-6 alpha-senecioyloxychaparrin (5), have been isolated from Simaba multiflora fruits. Their structures were deduced from spectral data. 1H-13C 2-D chemical-shift correlation nmr was applied to the structural elucidation of the antileukemic quassinoid 4.