RESUMEN
3',3'-Difluoro-3'-deoxythymidine (3) has been synthesized in four steps from thymidine, and characterized by 1H NMR and NOE experiments. The JHF coupling constants support a conformation in solution that is predominantly 2'-endo (S). Although conformationally and sterically nucleoside 3 may resemble other thymidine analogs which are active against HIV-1, 3 is virtually inactive.
Asunto(s)
Antivirales/farmacología , Didesoxinucleósidos/farmacología , VIH/efectos de los fármacos , Antivirales/síntesis química , Didesoxinucleósidos/síntesis química , Conformación Molecular , Relación Estructura-ActividadRESUMEN
Allyl methyl trisulfide (AMT), a constituent of garlic oil, was studied for its effects on glutathione S-transferase (GST) activity and on benzo[a]pyrene (BP)-induced neoplasia of the forestomach and lungs of female A/J mice. AMT induced increased GST activity in the forestomach, small bowel mucosa, liver, and lung. The forestomach and small bowel mucosa responded to a single low dose of AMT (3.0 mumol) given by oral intubation, whereas liver and lung were less reactive. A dose schedule of two administrations of 15 mumol AMT given 48 hours apart gave close-to-maximum induction in all four tissues and was chosen for investigation of its inhibitory effects. With this dose schedule, AMT produced an inhibition of BP-induced neoplasia of the forestomach as shown by a greater than 70% reduction in the number of tumors found at the completion of the experiment. Inhibition of pulmonary neoplasia did not occur. AMT is a member of a new class of naturally occurring chemicals that have the capacity to inhibit chemical carcinogenesis.