Research Abstract:
We are interested in the chemistry and biology of steroids. My laboratory specializes in natural products chemistry as it relates to the synthesis of steroids and steroid analogues. The compounds prepared in the laboratory are then studied in laboratories of colleagues throughout the university, and elsewhere, who share with us a common interest in the biological actions of steroids. Currently our efforts are focused in three main areas: neuroactive steroids; neuroprotective steroids; and cholesterol and bile steroid homeostasis.
Neuroactive steroids affect the functioning of ion-channels involved in synaptic transmission in the central nervous system. Some of these neuroactive steroids are potent anesthetics and the chemistry carried out on this project is designed either to provide mechanistic information on how steroids cause anesthesia or to provide new structure–activity data for the development of new anesthetic steroids.
Neuroprotective steroids are steroids that prevent or reduce neurodegeneration. We are interested in steroids that prevent neuronal cell death caused by oxidative damage.
The complex process whereby cells regulate the production and distribution of cholesterol and bile steroids in cells is incompletely understood. Steroids prepared in this project area are selected for their ability to provide a better understanding of this complex regulation.
Selected Publications:
Scaglione JB, Manion BD, Benz A, et al. Neurosteroid analogues. 11. Alternative ring system scaffolds: GABA modulatory and anesthetic actions of benz[f]indenes. J Med Chem 2006 49:4595-4605.
Westover EJ, Covey DF. Synthesis of ent-25-hydroxycholesterol. Steroids 2006 71:484-488.
Scaglione JB, Rath NP, Covey DF. First synthesis of enantiopure 1,6-difunctionalized dodecahydrobenz[f]indenes. J Org Chem 2005 70:1089-1092.
Zeng C, Manion BD, Benz A, et al. Neurosteroid Analogues 10. The effect of methyl group substitution at the C-6 and C-7 positions on the GABA modulatory and anesthetic actions of (3alpha,5alpha)- and (3alpha,5beta)-3-hydroxypregnane-20-one. J Med Chem 2005 48:3051-3059.
Jiang X, Manion BD, Benz A, et al. Neurosteroid Analogues. 9. Conformationally constrained pregnanes: Structure-activity studies of 13,24-cyclo-18,21-dinorcholane analogues of the GABA modulatory and anesthetic steroids (3alpha,5alpha)- and (3alpha,5beta)-3-hydroxypregnan-20-one. J Med Chem 2004 46:5334-5348.
Last Updated: 06/07/2007 |