RESUMEN
Plant natural products have historically been very important to drug discovery and development, particularly in the anticancer field. This is illustrated by a discussion of the structures and activities of camptothecin and its analogues, paclitaxel (Taxol), the vinca alkaloids vinblastine and vincristine, and podophyllotoxin and its analogues. A description of the isolation of one new and three known cardenolides from the Madagascar plant Pentopetia androsaemifolia is then provided as an example of this approach to drug discovery. The paper concludes with a brief discussion of betulinic acid, an old compound which is being developed into an anticancer and anti-HIV agent, and ipomoeassin F, an interesting antiproliferative compound isolated from a plant collected in Suriname.
Asunto(s)
Apocynaceae/química , Cardenólidos/farmacología , Proliferación Celular/efectos de los fármacos , Árboles/química , Cardenólidos/aislamiento & purificación , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Madagascar , Espectroscopía de Resonancia Magnética , Estructura Molecular , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Raíces de Plantas/química , Tallos de la Planta/químicaRESUMEN
Bioassay-guided fractionation of an ethanol extract of a Madagascar collection of the bark of Scutia myrtina led to the isolation of three new anthrone-anthraquinones, scutianthraquinones A, B and C (1-3), one new bisanthrone-anthraquinone, scutianthraquinone D (4), and the known anthraquinone, aloesaponarin I (5). The structures of all compounds were determined using a combination of 1D and 2D NMR experiments, including COSY, TOCSY, HSQC, HMBC, and ROESY sequences, and mass spectrometry. All the isolated compounds were tested against the A2780 human ovarian cancer cell line for antiproliferative activities, and against the chloroquine-resistant Plasmodium falciparum strains Dd2 and FCM29 for antiplasmodial activities. Compounds 1, 2 and 4 showed weak antiproliferative activities against the A2780 ovarian cancer cell line, while compounds 1-4 exhibited moderate antiplasmodial activities against P. falciparum Dd2 and compounds 1, 2, and 4 exhibited moderate antiplasmodial activities against P. falciparum FCM29.
Asunto(s)
Antraquinonas/química , Antimaláricos/química , Antineoplásicos Fitogénicos/química , Rhamnaceae/química , Animales , Antraquinonas/aislamiento & purificación , Antraquinonas/farmacología , Antimaláricos/aislamiento & purificación , Antimaláricos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Humanos , Madagascar , Corteza de la Planta/química , Extractos Vegetales/química , Plasmodium falciparum/efectos de los fármacosRESUMEN
Bioassay-guided fractionation of an ethanol extract of a Madagascar collection of Elaeodendron alluaudianum led to the isolation of two new cardenolide glycosides (1 and 2). The (1)H and (13)C NMR spectra of both compounds were fully assigned using a combination of 2D NMR experiments, including (1)H-(1)H COSY, HSQC, HMBC, and ROESY sequences. Both compounds 1 and 2 were tested against the A2780 human ovarian cancer cell line and the U937 human histiocytic lymphoma cell line assays, and showed significant antiproliferative activity with IC(50) values of 0.12 and 0.07 microM against the A2780 human ovarian cancer cell line, and 0.15 and 0.08 microM against the U937 human histiocytic lymphoma cell line, respectively.
Asunto(s)
Cardenólidos/aislamiento & purificación , Celastraceae/química , Proliferación Celular/efectos de los fármacos , Glicósidos/aislamiento & purificación , Cardenólidos/química , Cardenólidos/farmacología , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Ensayos de Selección de Medicamentos Antitumorales , Glicósidos/química , Glicósidos/farmacología , Humanos , Madagascar , Espectroscopía de Resonancia Magnética , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Bioassay-guided fractionation of an ethanol extract of a Madagascar collection of the fruits of Cordyla madagascariensis ssp. madagascariensis led to the isolation of the four new cassane diterpenoids 1-4. The 1H and 13C NMR spectra of all compounds were fully assigned using a combination of 2D NMR experiments, including COSY, HSQC, HMBC, and ROESY sequences. All of the isolates were tested against the A2780 human ovarian cancer cell line, and compounds 1 and 2 showed mild antiproliferative activity with IC50 values of 10 and 36 microM, respectively.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Diterpenos/aislamiento & purificación , Fabaceae/química , Plantas Medicinales/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Diterpenos/química , Diterpenos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Frutas/química , Humanos , Madagascar , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
A new cytotoxic hydroxybutanolide, tambouranolide, has been isolated by solid phase extraction from an ethanol extract of the dried roots of a species of Tambourissa (Monimiaceae) from the Madagascar rainforest. The structure was elucidated through the interpretation of spectral data and its comparison to data reported in the literature for related molecules. The compound showed moderate in vitro cytotoxicity with an IC50 of 8 micro g mL(-1) in the A2780 human ovarian cancer cell line assay.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Furanos/aislamiento & purificación , Monimiaceae/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Furanos/química , Furanos/farmacología , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Rotación Óptica , Raíces de Plantas/química , Extracción en Fase Sólida , Espectrometría de Masa Bombardeada por Átomos VelocesRESUMEN
Bioassay-guided fractionation of a crude ethanol extract from a Madagascar collection of Schizolaena hystrix afforded the two new long-chain compounds, 3 S-acetoxyeicosanoic acid ethyl ester ( 1) and 3 S-acetoxydoeicosanoic acid ( 2), and the known long-chain compound 3 S-acetoxyeicosanoic acid ( 3). In addition, the long-chain alcohol 1-hydroxydodecan-2-one ( 7), as well as the new flavonoid schizolaenone C ( 4) and the two known flavonoids diplacol ( 5) and 3'-prenylnaringenin ( 6) were isolated from a methanol extract of the same plant. Isolation and structure elucidation of the novel compounds and the cytotoxicities of all the isolates are reported.
Asunto(s)
Antineoplásicos Fitogénicos/toxicidad , Ácidos Eicosanoicos/toxicidad , Flavanonas/toxicidad , Magnoliopsida/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Fraccionamiento Químico , Ácidos Eicosanoicos/química , Ácidos Eicosanoicos/aislamiento & purificación , Flavanonas/química , Flavanonas/aislamiento & purificación , Humanos , Ácidos Láuricos/química , Ácidos Láuricos/aislamiento & purificación , Ácidos Láuricos/toxicidad , Madagascar , Clima TropicalRESUMEN
Bioassay-directed fractionation of an extract of the root and bark of Podocarpus madagascariensis resulted in the isolation of a new totarol diterpenoid (1) in addition to the three known cytotoxic diterpenoids 19-hydroxytotarol (2), totaradiol (3), and 4beta-carboxy-19-nor-totarol (4). The structure of the new compound 1 was established as methyl-13-hydroxy-14-isopropyl-9(11),12,14(8)-podocarpatriene-19-oate on the basis of 1D and 2D NMR spectroscopic interpretation and methylation of 4. All the compounds exhibited cytotoxic activity against the A2780 ovarian cancer cell line.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Cycadopsida/química , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Antineoplásicos Fitogénicos/química , Línea Celular Tumoral , Diterpenos/química , Ecosistema , Femenino , Humanos , Madagascar , Resonancia Magnética Nuclear Biomolecular , Neoplasias Ováricas/tratamiento farmacológico , Corteza de la Planta/química , Raíces de Plantas/química , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrofotometría Infrarroja , Espectrofotometría UltravioletaRESUMEN
Bioassay-directed fractionation of ethanol extracts of the roots and leaves of the plant Cassipourea madagascariensis resulted in the isolation of the two new terpenoids cassipourol (1) and cassipouryl acetate (2) in addition to the three known compounds, 3beta,30-dihydroxylup-20(29)-ene (3), 30-hydroxylup-20(29)-en-3-one (4), and combretol (5). The structures of the two new compounds were established on the basis of 1D and 2D NMR spectroscopic data and chemical conversion. All the isolated compounds were tested against the A2780 human ovarian cancer cell line; the two diterpenes (1 and 2) showed moderate cytotoxic activity, while the three known compounds (3-5) were weakly active.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Plantas Medicinales/química , Rhizophoraceae/química , Antineoplásicos Fitogénicos/química , Diterpenos/química , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Madagascar , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Hojas de la Planta , Células Tumorales CultivadasRESUMEN
Bioassay-guided fractionation of an ethanol extract of a Madagascar collection of Schizolaena hystrix afforded three new flavanones, schizolaenone A (1), schizolaenone B (2), and 4'-O-methylbonannione A (3), as well as three known flavanones, nymphaeol A, bonannione A, and macarangaflavanone B, and the flavanol bonanniol A. The structures of compounds 1-3 were determined by various one- and two-dimensional NMR techniques. All of the isolates were tested for cytotoxicity against the A2780 human ovarian cancer cell line. Nymphaeol A (IC(50) = 5.5 microg/mL) exhibited the greatest cytotoxicity, while the other flavanones were found to be only weakly active.