RESUMO
The Zimbabwean medicinal plant Monadenium lugardae was evaluated as a potential source of new anticancer constituents. Four new tetracyclic triterpene (1-4) were isolated, accompanied by four previously known triterpenes (5-8). Against a panel of human tumor cell lines, lugardstatins 1 (1) and 2 (2) had good cancer cell growth inhibitory activity. All of the triterpene structures (1-8) were established by 1D and 2D NMR spectrometric and HR mass spectrometric analysis.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Euphorbia/química , Plantas Medicinais/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Leucemia P388 , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Triterpenos/química , ZimbábueRESUMO
Cytotoxic constituents of the terrestrial plant Bridelia ferruginea were isolated using bioactivity-guided fractionation, which revealed the presence of the previously known deoxypodophyllotoxin (1), isopicrodeoxypodophyllotoxin (2), ß-peltatin (3), ß-peltatin-5-O-ß-D-glucopyranoside (3a), and the indole neoechinulin (4). As an extension of previous podophyllotoxin research, SAR studies were undertaken focused on 4-aza-podophyllotoxin structural modifications. A number of such derivatives were synthesized following modifications to the A and E rings. Such structural modifications with alkyl and 4-fluorobenzyl substituents at the 4-aza position provided the most potent cancer cell growth inhibitory activity (GI50 0.1 to <0.03 µg/mL) against a panel of six human cancer cell lines and one murine cancer cell line. Several compounds corresponding to 4'-demethylated modifications were also synthesized and found to be significantly less potent.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Euphorbiaceae/química , Podofilotoxina/farmacologia , Animais , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas , Humanos , Camundongos , Estrutura Molecular , Podofilotoxina/análogos & derivados , Podofilotoxina/síntese química , Podofilotoxina/química , Podofilotoxina/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
The purpose of this study was to attempt the reproducible coculture of more than two fungi for biosynthesis of potential antineoplastic substances. Five different fungi were simultaneously inoculated into broth cultures and grown for two weeks. Cancer cell line bioassay-guided fractionation, NMR, and mass spectroscopy led to the isolation and characterization of lateritin. Lateritin inhibited the growth of a mini-panel of human cancer cell lines, gram-positive bacteria, and Candida albicans. Individually, the five fungi did not synthesize detectable levels of lateritin. This study adds to the small but growing body of evidence that mixed fermentation is a viable avenue for natural product drug discovery. In addition, this is the first report of the reproducible coculture of more than two microbes for natural product biosynthesis, and the first report of the human solid tumor cell line and antimicrobial activities of lateritin.
Assuntos
Anti-Infecciosos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Fungos/metabolismo , Inibidores do Crescimento/isolamento & purificação , Morfolinas/isolamento & purificação , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Candida albicans/efeitos dos fármacos , Linhagem Celular Tumoral , Técnicas de Cocultura , Descoberta de Drogas , Fungos/isolamento & purificação , Bactérias Gram-Positivas/efeitos dos fármacos , Inibidores do Crescimento/biossíntese , Inibidores do Crescimento/farmacologia , Humanos , Morfolinas/metabolismo , Morfolinas/farmacologiaRESUMO
To further pursue the antineoplastic leads offered by our isolation of trans-dihydronarciclasine (1a) and 7-deoxy-trans-dihydronarciclasine (1c) from two medicinal plant species of the Amaryllidaceae family, a practical palladium-catalyzed hydrogenation procedure was developed for the synthesis of these isocarbostyrils from narciclasine (2a) and 7-deoxynarciclasine (2c).
Assuntos
Alcaloides/síntese química , Alcaloides/farmacologia , Antineoplásicos Fitogênicos/síntese química , Isoquinolinas/síntese química , Isoquinolinas/farmacologia , Narcissus/química , Plantas Medicinais/química , Alcaloides/química , Alcaloides de Amaryllidaceae , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Catálise , Isoquinolinas/química , Estrutura Molecular , Paládio/química , Fenantridinas , EstereoisomerismoRESUMO
By means of a five-step reaction sequence, narciclasine (2a), isolated from Narcissus sp., was converted to 10b(S)-epipancratistatin (3a) in 5.7% overall yield. The key step entailed a radical-initiated 10b,1 C-O cleavage employing tributyltin hydride to yield a B/C cis ring juncture (3b). Biological evaluation of 10b(S)-epipancratistatin (3a) provided evidence that antineoplastic activity was reduced by a factor of 10 when the B/C trans juncture was replaced with a B/C cis ring juncture.
Assuntos
Alcaloides de Amaryllidaceae/química , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Fenantridinas/química , Alcaloides de Amaryllidaceae/isolamento & purificação , Antineoplásicos Fitogênicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Narcissus/química , Fenantridinas/isolamento & purificação , Plantas Medicinais/química , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Bioassay-guided (P388 lymphocytic leukemia cell line) separation of extracts prepared from the leaves, stems, and pods of Bauhinia purpurea, and, in parallel, its roots, led to the isolation of four new dibenz[b,f]oxepins (2a, 3-5) named bauhiniastatins 1-4, as well as the known and related pacharin (1) as cancer cell growth inhibitors. The occurrence of oxepin derivatives in nature is quite rare. Bauhiniastatins 1-4 were found to exhibit significant growth inhibition against a minipanel of human cancer cell lines, and bauhiniastatin 1 (2a) was also found to inhibit the P388 cancer cell line. Structures for these new cancer cell growth inhibitors were established by spectroscopic techniques that included HRMS and 2D NMR.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Bauhinia/química , Benzoxepinas/isolamento & purificação , Plantas Medicinais/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Benzoxepinas/química , Benzoxepinas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Índia , Leucemia P388 , Camundongos , Estrutura Molecular , Raízes de Plantas/química , Células Tumorais CultivadasRESUMO
As an extension of structure-activity relationship studies of pancratistatin (1), various techniques were first evaluated for separating the mixtures of 7-deoxynarciclasine (2b) and 7-deoxy-trans-dihydronarciclasine (3a) isolated from Hymenocallis littoralis. An efficient solution for that otherwise difficult separation then allowed the lactam carbonyl group of protected (4c and 5c) alcohols 2b and 3a to be reduced employing lithium aluminum hydride. Cleavage (TBAF followed by H2SO4) of the silyl ester/acetonide protected 6a gave amine 8. X-ray crystal structure determinations were employed to confirm the structures of 3,4-acetonide-5-aza-6-deoxynarciclasine (6b), 5-aza-6-deoxynarciclasine (8a), and 5-aza-6-deoxy-trans-dihydronarciclasine (9a, 9b). Against the murine P388 lymphocytic leukemia and a panel of human cancer cell lines, the parent natural products, 7-deoxynarciclasine (2b) and 7-deoxy-trans-dihydronarciclasine (3a), were found to generally be more cancer cell growth inhibitory (GI50 0.1 to <0.01 microg/mL) than the compounds with structural modifications such as amine 8 by a factor of 10 or more. The trans ring juncture of isocarbostyril 3a proved to be an important modification of narciclasine (2a) for improving cancer cell growth inhibition in this series.
Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Isoquinolinas/química , Isoquinolinas/isolamento & purificação , Narcissus/química , Plantas Medicinais/química , Alcaloides de Amaryllidaceae , Animais , Antineoplásicos Fitogênicos/farmacologia , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Isoquinolinas/farmacologia , Leucemia P388 , Camundongos , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
[structure: see text] Effective, scalable total syntheses and biological evaluation of six phorboxazole A analogues (1-6) have been achieved. Importantly, the C(45-46)-saturated, C(45-46)-alkenyl, and the C(45-46)-E-chloroalkenyl congeners (4, 5, and 6, respectively) reveal low nanomolar tumor cell growth inhibitory activity (GI50's) similar to or, in some cell lines, greater than that of the phorboxazoles across a diverse panel of human cancer cell lines.
Assuntos
Carbono/química , Compostos Heterocíclicos de 4 ou mais Anéis/síntese química , Compostos Heterocíclicos de 4 ou mais Anéis/toxicidade , Oxazóis/síntese química , Oxazóis/toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Compostos Heterocíclicos de 4 ou mais Anéis/química , Humanos , Estrutura Molecular , Oxazóis/química , Relação Estrutura-AtividadeRESUMO
The CH3OH-CH2Cl2 extract of an Indian collection (entire plant) of Gynandropsis gynandra (L.) Briq. was separated based on bioassay results employing cancer cell lines. Six cancer cell growth inhibitors were isolated and found to be known flavone apegenin (4) and flavonols 1-3, 5, and 6. The structure of flavonol 2 was confirmed by X-ray crystal structure determination. All of the five flavonols (1-3, 5, 6) inhibited the murine P388 lymphocytic leukemia cell line with ED50 values of 3.0, 9.2, 4.0, 0.37, and 3.9 microg/ml, respectively. All six of the flavonoids (1-6) also exhibited activity against a panel of six human cancer cell lines. Penduletin (3) inhibited growth of the Gram-negative pathogen Neisseria gonorrhoeae and apegenin (4) inhibited growth of the Gram-positive opportunist Enterococcus faecalis.
Assuntos
Avaliação Pré-Clínica de Medicamentos , Animais , Anisotropia , Anti-Infecciosos/farmacologia , Bioensaio , Linhagem Celular Tumoral , Proliferação de Células , Cristalografia por Raios X , Enterococcus faecalis/metabolismo , Flavonas , Flavonóis/química , Humanos , Ligação de Hidrogênio , Camundongos , Modelos Químicos , Modelos Moleculares , Neisseria gonorrhoeae/metabolismo , Extratos Vegetais/farmacologia , Plantas Medicinais/metabolismo , Células Tumorais CultivadasRESUMO
Using bioactivity-directed isolation procedures, three new spirostanol saponins designated sansevierin A (1), sansevistatin 1 (2), and sansevistatin 2 (3) were isolated (10(-5) % yield) from the CH3OH-CH2Cl2 extract of Sansevieria ehrenbergii, accompanied by three known steroidal saponins (4-6). The structures were determined on the basis of chemical methods and spectroscopic analysis, especially 1D and 2D NMR experiments. Each of the saponins was evaluated against the P388 lymphocytic leukemia cell line and a panel of human cancer cell lines. Except for 1, all were found to cause inhibition of cancer cell growth. In addition, most of the saponins exhibited antimicrobial activity, particularly against the pathogenic fungi Candida albicans and Cryptococcus neoformans.
Assuntos
Antifúngicos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Plantas Medicinais/química , Sansevieria/química , Saponinas/isolamento & purificação , Espirostanos/isolamento & purificação , Animais , Antifúngicos/química , Antifúngicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Candida albicans/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Quênia , Leucemia P388 , Saponinas/química , Saponinas/farmacologia , Espirostanos/química , Espirostanos/farmacologia , Células Tumorais CultivadasRESUMO
The synthesis of sodium narcistatin (8) was improved (88% overall yield) and the modified reaction sequence was utilized to synthesize three new 3,4-cyclic phosphate prodrugs, sodium 7-deoxynarcistatin (5), sodium 7-deoxy-trans-dihydronarcistatin (6), and sodium trans-dihydronarcistatin (7). The human cancer cell line inhibitory isocarbostyril precursors were isolated from the bulbs of Hymenocallis littoralis obtained by horticultural production or reduction of narciclasine (1a --> 4) from the same source.
Assuntos
Antineoplásicos Fitogênicos/síntese química , Compostos Heterocíclicos de 4 ou mais Anéis/síntese química , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Liliaceae/química , Estrutura Molecular , Fenantridinas/química , Fenantridinas/farmacologia , Plantas Medicinais/químicaAssuntos
Alcaloides de Amaryllidaceae/química , Antineoplásicos Fitogênicos/síntese química , Carbolinas/síntese química , Plantas Medicinais/química , Antineoplásicos Fitogênicos/farmacologia , Carbolinas/farmacologia , Ligação de Hidrogênio , Isoquinolinas/química , Mimetismo Molecular , Estrutura Molecular , EstereoisomerismoRESUMO
The yellow cedar tree, Chamaecyparis nootkatensis, collected in southeast Alaska was evaluated as a potential source of new anticancer agents. Two new diterpene anticancer constituents termed nootkastatins 1 (4) and 2 (5) were isolated along with three previously known diterpene cancer cell growth inhibitors where two were reported as synthetic modifications of totarol and not previously found in nature. All five diterpene structures were established by HRMS and 1D and 2D NMR spectroscopic analyses combined with three X-ray crystal structure determinations (2, 3, and 5). Against a panel of six human cancer cell lines, this series of diterpenes exhibited inhibition over the range GI(50) 0.75-2.0 microg/mL, and all inhibited the growth of Gram-positive bacteria and fungi.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Chamaecyparis/química , Diterpenos/isolamento & purificação , Plantas Medicinais/química , Alaska , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Fungos/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Leucemia P388 , Camundongos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Árvores/química , Células Tumorais CultivadasRESUMO
A bioassay-guided investigation of Gustavia hexapetala led to the isolation of a new cancer cell growth inhibitor designated gustastatin (1) and four previously known cancer cell growth inhibitors that included betulinic acid (2). The structures were assigned on the basis of analyses of HRMS combined with 1D and 2D NMR data. The structure of portentol (5) was confirmed by an X-ray crystal structure determination.
Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Lecythidaceae/química , Ácido Oleanólico/análogos & derivados , Fenóis/química , Fenóis/isolamento & purificação , Plantas Medicinais/química , Animais , Antineoplásicos Fitogênicos/farmacologia , Brasil , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Leucemia P388 , Camundongos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Triterpenos Pentacíclicos , Fenóis/farmacologia , Árvores , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Ácido BetulínicoRESUMO
Selective phosphorylation of phenpanstatin (3a) with tetrabutylammonium dihydrogen phosphate and dicyclohexylcarbodiimide in pyridine followed by cation-exchange chromatographic procedures was found to provide an efficient route to a new series (3b-3d) of promising 3,4-O-cyclic phosphate prodrugs designated phenpanstatin phosphates. Application of analogous reaction conditions to pancratistatin (1a) led to a mixture of monophosphate derivatives where sodium pancratistatin 4-O-phosphate (4a) was isolated and the structure confirmed by X-ray crystallography. Modification of the reaction conditions allowed direct phosphorylation of pancratistatin followed by cation-exchange chromatography to afford sodium pancratistatin 3,4-O-cyclic phosphate (5a), which was selected for preclinical development.
Assuntos
Alcaloides de Amaryllidaceae , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/síntese química , Isoquinolinas/química , Pró-Fármacos/síntese química , Cromatografia por Troca Iônica , Cristalografia por Raios X , Estrutura Molecular , Fosforilação , Plantas Medicinais/químicaRESUMO
Bioassay (P388 lymphocytic leukemia cell line and human tumor cell lines)-guided separation of the extracts prepared from the tropical and coastal trees Hernandia peltata (Malaysia) and Hernandianymphaeifolia (Republic of Maldives) led to the isolation of a new lignan designated as hernanol (1) and 12 previously known lignans: (-)-deoxypodophyllotoxin (2), deoxypicropodophyllin (3), (+)-epiaschantin (4), (+)-epieudesmin (5), praderin (6), 5'-methoxyyatein (7), podorhizol (8), deoxypodorhizone (9), bursehernin (10), kusunokinol (11), clusin (12), and (-)-maculatin (13). The oxidative cyclization (with VOF(3)) of lignans 8, 9, and 10 resulted in a new and unusual benzopyran (14), isostegane (15), and a new dibenzocyclooctadiene lactone (16), respectively. The structure and relative stereochemistry of hernanol (1) and lignans 3, 7, 8, 9, 10, 11, and 12 were determined by 1D and 2DNMR and HRMS analyses. The structures and absolute stereochemistry of structures 2, 4, 5, 6, 13, 14, 15, and 16 were unequivocally determined by single-crystal X-ray diffraction analyses. Evaluation against the murine P388 lymphocytic leukemia cell line and human tumor cell lines showed podophyllotoxin derivatives 2 and 3 to be strong cancer cell line growth inhibitors and substances 4, 5, 8, and 15 to have marginal cancer cell line inhibitory activities. Seven of the lignans and one of the synthetic modifications (14) inhibited growth of the pathogenic bacterium Neisseria gonorrhoeae.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Lignanas/isolamento & purificação , Plantas Medicinais/química , Árvores/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ilhas do Oceano Índico , Leucemia P388 , Lignanas/química , Lignanas/farmacologia , Malásia , Camundongos , Testes de Sensibilidade Microbiana , Conformação Molecular , Estrutura Molecular , Neisseria gonorrhoeae/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
Bioassay (P388 lymphocytic leukemia cell line and human cancer cell lines)-guided separation of an extract prepared from the stem bark and twigs of the previously uninvestigated Ruprechtia tangarana led to the isolation of a new isocarbostyril designated ruprechstyril (1), secalonic acid A (2), 2'-O-methylevernic acid (3), 3,3',4-tri-O-methylflavellagic acid (4), lichexanthone (5), methyl asterrate (6), and 3beta,22E,24S-stigmasta-5,22-dien-3-ol (7). Only secalonic acid A exhibited cancer cell and microbial growth inhibition. The structure of ruprechstyril (1) was determined by HRMS and 1D and 2D NMR spectra and confirmed by single-crystal X-ray analysis. The structures and absolute stereochemistry of five of the other compounds were also established by X-ray crystal structure determination.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Hidroxiquinolinas/isolamento & purificação , Plantas Medicinais/química , Polygonaceae/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Hidroxiquinolinas/química , Hidroxiquinolinas/farmacologia , Leucemia P388 , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Peru , EstereoisomerismoRESUMO
Cancer cell line bioassay-guided separation of an extract from a Yukon Territory fungus resulted in the isolation of a new C(16)-terpene dilactone designated yukonin (1) accompanied by two previously known, structurally related constituents (2 and 3). The structure of each was determined by X-ray crystallographic analysis. Dilactone 2 was found to correspond to LL-Z1271alpha isolated from fungi in the genera Oidiodendron, Acrostalagmus, and Holwaya, while dilactone 3 had earlier been prepared by reduction of an alpha-lactol derivative. Each of the dilactones was found to inhibit growth of human cancer cell lines (pancreas, breast, CNS, lung, colon, and prostate) and some pathogenic fungi.
Assuntos
Antineoplásicos/isolamento & purificação , Lactonas/isolamento & purificação , Phialophora/química , Plantas Medicinais/química , Terpenos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/farmacologia , Candida albicans/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lactonas/química , Lactonas/farmacologia , Conformação Molecular , Estrutura Molecular , Terpenos/química , Terpenos/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacos , YukonRESUMO
An efficient procedure was found for synthetic conversion of the sparingly soluble anticancer isocarbostyril narciclasine (1), a component of various Narcissus species, to a cyclic phosphate designated narcistatin (3b). The reaction between narciclasine, tetrabutylammonium dihydrogen phosphate, and p-toluenesulfonic acid in pyridine afforded pyridinium narcistatin (3a) in reasonable yields. Transformation of narcistatin (3a) to, for example, the water-soluble prodrug sodium narcistatin (3d) was easily achieved by cation exchange chromatography. Narcistatin (3b) and 15 salt derivatives were evaluated against a panel of human cancer cell lines, and the range (0.1-0.01) of GI(50) values in micro g/mL was found to parallel that shown by the parent narciclasine.
Assuntos
Alcaloides/química , Alcaloides de Amaryllidaceae , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/síntese química , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Narcissus/química , Compostos Organofosforados/síntese química , Compostos Organofosforados/farmacologia , Fenantridinas , Plantas Medicinais/química , Pró-Fármacos/síntese química , Animais , Divisão Celular/efeitos dos fármacos , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Leucemia P388 , Camundongos , Conformação Molecular , Estrutura Molecular , Organofosfatos/síntese química , Organofosfatos/farmacologia , Pró-Fármacos/farmacologia , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
The bark of the giant neem tree Melia dubia was found to contain 11 euphane-type triterpenes. Five new compounds, meliastatins 1-5 (1-5), proved to inhibit growth of the P388 lymphocytic leukemia cell line (ED(50) 1.7-5.6 microg/mL). Four of the others, the previously known methyl kulonate (8), kulinone (9), 16-hydroxybutyrospermol (10), and kulactone (11), were also found to inhibit (ED(50) 2.5-6.2 microg/mL) the P388 cancer cell line. In addition, two new euphane triterpenes were isolated and named dubione A (6) and dubione B (7). Structures for each of the 11 euphane triterpenes were established by spectral techniques that included HRMS and 2D NMR.