RESUMO
The reaction of 16 alpha,17 alpha-epoxy-3 beta-hydroxy-5-pregnen-20-one with 6-methyl thiopurine activated with sodium hydride leads to the coupling of the purine base with the carbonyl group at C-20 to give a steroidal nucleoside analog, which is termed "nucleosteroid." In the presence of an excess of purine, a parallel reaction occurs in which the oxirane ring is opened, presumably by nucleophilic attack of an intermediate C-20 oxyanion, and yields as the main product of reaction an oligomeric mixture of nucleosteroid units linked together by ether linkages. Analogous reactions conducted with 3 beta-hydroxy-5-pregnen-20-one and with 3 beta,17 alpha-dihydroxy-5-pregnen-20-one gave minor amounts or only traces of the corresponding coupling adduct, and oligomerization did not occur. This behavior is interpreted in terms of the conformational differences showed by the different steroids to the attack by the purine.
Assuntos
Purinas/química , Esteroides/química , Acetilação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Mercaptopurina/análogos & derivados , Mercaptopurina/química , Estrutura Molecular , Pregnenos/químicaRESUMO
Despite the major advances of cancer chemotherapy during the past 40 years, host toxicities and drug resistance justify the need to continue the search for new antineoplastic agents. In the present work, we have studied the effect of six synthetic drugs on the in vitro growth of two murine mammary adenocarcinomas (M3 and MM3), as well as on normal embryonic cells. AI, MIC and MPI are purines coupled to a sulfonylated inositol, while DIC and DEI have nitrogen mustard as substituent. Methylsulfonylmucoinositol was the common substituent. Our results indicated that only drugs substituted with nitrogen mustards had an antiproliferative effect. DEI was more effective on tumor cells than on normal cells.