RESUMEN
Betulinic acid (BA, 3ß-hydroxy-lup-20(29)-en-28-oic acid) is a pentacyclic triterpene acid present predominantly in Betula ssp. (Betulaceae) and is also widely spread in many species belonging to different plant families. BA presents a wide spectrum of remarkable pharmacological properties, such as cytotoxic, anti-HIV, anti-inflammatory, antidiabetic and antimicrobial activities, including antiprotozoal effects. The present review first describes the sources of BA and discusses the chemical strategies to produce this molecule starting from betulin, its natural precursor. Next, the antiprotozoal properties of BA are briefly discussed and the chemical strategies for the synthesis of analogues displaying antiplasmodial, antileishmanial and antitrypanosomal activities are systematically presented. The antiplasmodial activity described for BA was moderate, nevertheless, some C-3 position acylated analogues showed an improvement of this activity and the hybrid models-with artesunic acid-showed the most interesting properties. Some analogues also presented more intense antileishmanial activities compared with BA, and, in addition to these, heterocycles fused to C-2/C-3 positions and amide derivatives were the most promising analogues. Regarding the antitrypanosomal activity, some interesting antitrypanosomal derivatives were prepared by amide formation at the C-28 carboxylic group of the lupane skeleton. Considering that BA can be produced either by isolation of different plant extracts or by chemical transformation of betulin, easily obtained from Betula ssp., it could be said that BA is a molecule of great interest as a starting material for the synthesis of novel antiprotozoal agents.
Asunto(s)
Antiprotozoarios/síntesis química , Antiprotozoarios/farmacología , Triterpenos Pentacíclicos/síntesis química , Triterpenos Pentacíclicos/farmacología , Antiprotozoarios/química , Modelos Moleculares , Triterpenos Pentacíclicos/química , Triterpenos/química , Ácido BetulínicoRESUMEN
This paper reports on the syntheses and spectrometric characterisation of eleven novel ent-kaurane diterpenoids, including a complete set of (1)H, (13)C NMR and crystallographic data for two novel ent-kaurane diepoxides. Moreover, the antineoplastic cytotoxicity for kaurenoic acid and the majority of ent-kaurane derivatives were assessed in vitro against a panel of fourteen cancer cell lines, of which allylic alcohols were shown to be the most active compounds. The good in vitro antimalarial activity and the higher selectivity index values observed for some ent-kaurane epoxides against the chloroquine-resistant W2 clone of Plasmodium falciparum indicate that this class of natural products may provide new hits for the development of antimalarial drugs.
Asunto(s)
Antimaláricos/farmacología , Antineoplásicos/farmacología , Diterpenos de Tipo Kaurano/farmacología , Plasmodium falciparum/efectos de los fármacos , Antimaláricos/síntesis química , Antimaláricos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Diterpenos de Tipo Kaurano/síntesis química , Diterpenos de Tipo Kaurano/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Modelos Moleculares , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Relación Estructura-ActividadRESUMEN
A recent reinvestigation of aerial parts of Wedelia paludosa D.C. is described and reports, for the first time, the isolation of iso-kaurenoic acid from this species.
Asunto(s)
Diterpenos/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Wedelia/química , Diterpenos/química , Diterpenos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
A recent reinvestigation of aerial parts of Wedelia paludosa D.C. is described and reports, for the first time, the isolation of iso-kaurenoic acid from this species.
Uma recente reinvestigação das partes aéreas de Wedelia paludosa D.C. é descrita e relata, pela primeira vez, o isolamento do ácido iso-caurenóico desta espécie.
Asunto(s)
Diterpenos/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Wedelia/química , Diterpenos/química , Diterpenos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
Several new prenylnaphthohydroquinone derivatives have been prepared through the Diels-Alder condensation between alpha-myrcene and 1,2-benzoquinone and evaluated for their cytotoxic activity against A-549, HT-29 and MB-231 cultured cell lines. All of them have shown GI50 values in the microM level.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/toxicidad , Naftoquinonas/química , Naftoquinonas/toxicidad , Prenilamina/análogos & derivados , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Isomerismo , Estructura Molecular , Naftoquinonas/síntesis química , Prenilamina/síntesis química , Prenilamina/química , Prenilamina/toxicidadRESUMEN
Several acetyl derivatives of prenylnaphthohydroquinone have been synthetized and evaluated for their cytotoxicity against A-549 human lung carcinoma and H-116 human colon carcinoma neoplastic cells. The IC50 values against A-549 are compared with those observed for previously reported unsubstituted derivatives.