RESUMEN
The spirostanic steroidal side-chain of diosgenin and hecogenin was modified to produce 22-oxocholestane derivatives. This type of side-chain was obtained in good yields through a straightforward four-step pathway. These compounds show potent brassinosteroid-like growth promoting activity evaluated via the rice lamina joint inclination bioassay. This is the first report of steroidal skeletons bearing the 22-oxocholestane side-chain and preserving the basic structure (A-D rings) from their corresponding parent compounds acting as plant growth promoters.
Asunto(s)
Colestanos , Oryza/crecimiento & desarrollo , Reguladores del Crecimiento de las Plantas , Colestanos/síntesis química , Colestanos/química , Colestanos/farmacología , Reguladores del Crecimiento de las Plantas/síntesis química , Reguladores del Crecimiento de las Plantas/química , Reguladores del Crecimiento de las Plantas/farmacologíaRESUMEN
The synthesis and biological evaluation of three new cholestane frameworks of the type: (25R)-3ß,16ß-Diacetoxy-23-ethylidene-26-hydroxy-22-oxocholestane, starting from spirostanic sapogenins of the 25R series, is described. The compounds were obtained by the reductive cleavage of the F ring of 22-oxo-23(1),26-epoxycholestane derivatives using 9-BBN. These modified derivatives exhibit cytotoxic activity against CEM and MCF7 cells and are able to induce apoptosis in them. Its effect on the cell cycle was determined.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Colestanos/síntesis química , Colestanos/farmacología , Sapogeninas/química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Caspasa 7/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Técnicas de Química Sintética , Colestanos/química , HumanosRESUMEN
In this article, we describe the application of lipases in acylation and alcoholysis reactions on steroids and nucleosides. In the field of steroids, a variety of acetyl and fatty acid derivatives of androstanes, pregnanes, and cholestanes have been prepared through lipase-catalyzed acylation and alcoholysis reactions taking advantage of the high regio- and stereoselectivity of these enzymes. The substrates as well as the products show a high degree of biological activity as neurosteroids, hormones, and glucocorticoids. The regioselective preparation of diacylated nucleosides by means of an enzymatic alcoholysis allowed the synthesis of nucleosides prodrugs or modified nucleosides. The quantitative full deacylation and dealkoxycarbonylation of nucleosides and steroids is a mild synthetic method for the deprotection of these labile compounds. Some of the reported steroid and nucleoside products are novel, and it is not possible to obtain them satisfactorily by following traditional synthetic procedures. The advantages presented by this methodology, such as selectivity, mild reaction conditions, and low environmental impact, make the lipases an important tool in the application of the principles of Green Chemistry, offering a convenient way to prepare derivatives of natural compounds with a great potential in the pharmaceutical industry.
Asunto(s)
Productos Biológicos/síntesis química , Proteínas Fúngicas/química , Lipasa/química , Nucleósidos/química , Acilación , Androstanos/síntesis química , Biocatálisis , Candida/química , Colestanos/síntesis química , Ácidos Grasos/química , Tecnología Química Verde , Pregnanos/síntesis química , Profármacos/síntesis química , EstereoisomerismoRESUMEN
In a previous work our group showed that some synthetic stigmastanes may play a role in immune-mediated inflammation. In this paper we report the syntheses of a series of new steroidal compounds derived from dehydroepiandrosterone and stigmasterol, and the evaluation of their in vitro inhibitory activity of the TNF-alpha production by macrophages. A preliminary qualitative structure-activity relationship was established.