RESUMEN
The aim of this review is to update current knowledge on the betulinic, ursolic and echinocystic acids and their natural and semisynthetic analogs, focussing on their cytotoxic and anti-HIV activities. Then, the last results of the authors' team on unusual semisynthetic derivatives of these triterpenoids will be presented in order to establish structure/activity relationships.
Asunto(s)
Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Ácido Oleanólico/análogos & derivados , VIH-1/efectos de los fármacos , Células HT29 , Humanos , Estructura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/farmacología , Triterpenos Pentacíclicos , Relación Estructura-Actividad , Triterpenos/química , Triterpenos/farmacología , Células Tumorales Cultivadas/efectos de los fármacos , Ácido Betulínico , Ácido UrsólicoRESUMEN
The isolation of 14 known triterpenoids and phytosterols from the trunk bark of Maquira coriacea, and complete spectral data of a cardenolide, k-strophanthin-beta (1), are reported.
Asunto(s)
Cardenólidos/química , Moraceae , Fitoterapia , Extractos Vegetales/química , Triterpenos/química , Humanos , Espectroscopía de Resonancia MagnéticaRESUMEN
Bidentatoside II(1) and chikusetsusaponin V methyl ester (2) are two further triterpene saponins isolated from the roots of Achyranthes bidentata. Chemical and homo and heteronuclear two-dimensional (2D) NMR techniques have led to the structural elucidation of 1 which is a new seco-glycoside of oleanolic acid and the full 1H- and 13C-NMR assignments of 2. These compounds did not show any potentiation of the in vitro cytotoxicity of cisplatin in the HT 29 human colon cancer cell line.
Asunto(s)
Achyranthes/química , Saponinas/química , Triterpenos/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Células HT29/efectos de los fármacos , Humanos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/química , Saponinas/aislamiento & purificación , Saponinas/farmacología , Triterpenos/aislamiento & purificación , Triterpenos/farmacologíaRESUMEN
From the rhizomes of Dioscorea cayenensis Lam.-Holl (Dioscoreaceae), the new 26- O- beta- D-glucopyranosyl-22-methoxy-3 beta,26-dihydroxy-25( R)-furost-5-en-3- O- alpha- L-rhamnopyranosyl-(1-->4)- alpha- L-rhamnopyranosyl-(1-->4)-[ alpha- L-rhamnopyranosyl-(1-->2)]- beta- D-glucopyranoside ( 1) was isolated together with the known dioscin ( 2) and diosgenin 3- O- alpha- L-rhamnopyranosyl-(1-->4)- alpha- L-rhamnopyranosyl-(1-->4)-[ alpha- L-rhamnopyranosyl-(1-->2)]- beta- D-glucopyranoside ( 3). Their structures were established on the basis of spectral data. Compound 2 exhibited antifungal activity against the human pathogenic yeasts Candida albicans, C. glabrata and C. tropicalis (MICs of 12.5, 12.5 and 25 micro g/mL, respectively) whereas 3 showed weak activity and 1 was inactive.
Asunto(s)
Antifúngicos/farmacología , Candida/efectos de los fármacos , Dioscorea , Fitoterapia , Extractos Vegetales/farmacología , Esteroides/farmacología , Antifúngicos/administración & dosificación , Antifúngicos/química , Antifúngicos/uso terapéutico , Humanos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Raíces de Plantas , Esteroides/administración & dosificación , Esteroides/química , Esteroides/uso terapéuticoRESUMEN
The antiplasmodial activity of twelve alkaloids with an aspidospermane skeleton was estimated in vitro on chloroquine-resistant and sensitive strains of Plasmodium falciparum. Seven tetracyclic alkaloids possessing a free ethyl chain such aspidospermine, showed IC50 after incubation for 72 h between 3.2 and 15.4 microM. Moreover, four pentacyclic alkaloids with ethyl chain included in a tetrahydrofuran, such haplocine, showed a reduced activity, with IC50, after 72 h, between 22.6 and 52.6 microM. According to these results, a chloroquine-potentiating experiment was also performed with two of the most active compounds. Isobolograms were obtained and demonstrated a synergic effect of N-formyl-aspidospermidine and aspidospermine when associated with chloroquine. The cytotoxicity and the selectivity index of some alkaloids were also estimated.
Asunto(s)
Antimaláricos/farmacología , Aspidosperma , Alcaloides Indólicos/farmacología , Plasmodium falciparum/efectos de los fármacos , Quinolinas , Alcaloides/farmacología , Animales , Antimaláricos/química , Línea Celular , Cloroquina/farmacología , Resistencia a Medicamentos , Humanos , Hipoxantina/farmacología , Alcaloides Indólicos/química , Indoles/farmacología , Concentración 50 Inhibidora , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/farmacología , Relación Estructura-Actividad , Pruebas de ToxicidadRESUMEN
Bidentatoside I (1) is a new triterpene saponin bearing an unusual dioxopropionic acid unit, isolated from the roots of Achyranthes bidentata. Structural elucidation was performed mainly by chemical and homo- and heteronuclear 2D NMR techniques. This compound did not show any potentiation of the in vitro cytotoxicity of cisplatin in the HT 29 human colon cancer cell line.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Magnoliopsida/química , Saponinas/aislamiento & purificación , Triterpenos/aislamiento & purificación , Antineoplásicos/farmacología , Neoplasias del Colon/tratamiento farmacológico , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Espectroscopía de Resonancia Magnética , Modelos Químicos , Saponinas/farmacología , Triterpenos/farmacología , Células Tumorales CultivadasRESUMEN
Fifteen new ursolic and betulinic triterpenoids, bearing various functionalities at C-3 and C-28 were synthesized as potential cytotoxic agents. All compounds were obtained by a hemisynthetic route via ursolic and betulinic acids. Preliminary screening of these compounds on human HT 29 colon cancer cells revealed inhibitory activity for three of them. Beta-D-Glucopyranosyl-3beta-hydroxyurs-12(13)-en-28-oate 1c, 3beta-3-(3-pyridyl)-prop-2-enoyloxyurs-12(13)-en-28-oic acid 1i and the potassium salt of 3beta-cinnamoyloxylup-20(29)-en-28-oic acid 2d demonstrated cytotoxic activity in the micromolar range: 8.0, 45.0 and 8.0 microM, respectively.