congresos y reuniones científicas
Study of glucocorticoid activity of 21-Hemisuccinate-6,19-OP, an oxygen bridge analog
ALVAREZ, L; VELEIRO, A.; LANTOS, C.P.; PECCI, A.; BURTON, G.
Congreso; XLII Reunión Anual de SAIB; 2006
According to the overall conformation as the three-dimensional structure and spatial distribution of charges, glucocorticoid molecules exhibit a bent skeleton as a consequence of the degree of curvature at the A/B junction of the respective structure. In our approach rigidly bent analogue with some specific anti-glucocorticoid activities was obtained by a 6,19 oxygen bridge introduced in a pregnane structure(21-OH-6,19-OP). This compound devoids affinity at receptoral level forboth mineralocorticoid and progesterone receptor. In order to enhance polarity and water solubility we synthesized the esther derivative 21-hemisuccinate-6,19-OP. This new compound has demonstrated to be a highly potent antiapoptotic agent, according to DNA fragmentation and FICT-Annexin V assays when it is co-administrated in combination to dexamethasone in thymocyte primary cultures. However, this compound not only is not able to block dexamethasone induced MMTV-luciferase reportergene but also it significantly potenciates at its lowest concentration the glucocorticoid action of dexamethasone.