RESUMEN
Natural products of the naphthoquinone spiroketal structural type served as lead structures for the development of novel inhibitors of the thioredoxin-thioredoxin reductase redox system. The most potent compound in this series inhibited thioredoxin with an IC(50) of 350 nM, and many derivatives showed low micromolar activities for growth inhibition against two breast cancer cell lines.
Asunto(s)
Naftoquinonas/farmacología , Reductasa de Tiorredoxina-Disulfuro/antagonistas & inhibidores , Tiorredoxinas/antagonistas & inhibidores , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , División Celular/efectos de los fármacos , Dioxanos/síntesis química , Dioxanos/química , Dioxanos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Compuestos Epoxi/síntesis química , Compuestos Epoxi/química , Compuestos Epoxi/farmacología , Humanos , Naftalenos , Naftoquinonas/síntesis química , Naftoquinonas/química , Compuestos de Espiro/síntesis química , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , Células Tumorales CultivadasRESUMEN
Twenty-eight Simmental bull calves were randomly allotted to one of three treatments at birth. Ten bulls (IB) and nine steers (IS), castrated within 3 days of birth, were implanted with oestradiol (E(2)). The remaining calves were non-implanted, control bulls (CB). Calves were implanted within 3 days of birth and at 200-day intervals until slaughter at 14·8 months of age and at a mean carcass weight of 381·6 kg. Blood samples were taken every 14 days from 9·8 through 14·8 months and serum was analyzed for E(2) and testosterone (T) levels. Carcasses were chilled in a 3 to 7°C cooler. Carcass data were obtained and aged longissimus dorsi steaks were evaluated by a trained sensory panel and a Warner-Bratzler shear (WBS) device. Scrotal circumferences were smaller (P < 0·0.5) for IB than for CB. Control bulls had heavier weaning weights (P < 0·05) than IB and higher (P < 0·05) feedlot gains than IS. Implanted steers required more (P < 0·05) feed/unit of gain than CB and IB. Implanting bulls with E(2) increased (P < 0·05) serum E(2) levels and tended (P < 0·10) to reduce T levels. Serum E(2) in IS and IB were drastically increased (P < 0·05) for 4 to 6 weeks following re-implantation during the feedlot phase, then sharply declined. Implanted steer carcasses had more youthful maturity scores than CB carcasses. The incidence of hear ring (dark, coarse, band formation) was greater (P < 0·05) for IB than for IS, probably because of the thinner fat cover (P < 0·05) on IB. Ribeye areas were smaller (P < 0·05) and yield grades were higher for IS than for CB. Testicle weights were not significantly different between IB and CB, although variability was greater for IB. Carcass masculinity was least (P < 0·05) for IS, and IB were less (P < 0·05) masculine than CB. The only difference in longissimus dorsi sensory traits was that steaks from IB were juicier than steaks from CB. Also, WBS values were lower (P < 0·05) for IS than for CB.
