Abstract: The present invention features novel withanolides, as well as analogs and salts thereof, for use in the treatment of proliferative disease, cardiovascular disease, neurodegenerative disease and inflammatory disease.

Abstract: A group of indolealkylamino-withasteroid conjugates, isolated and purified from Withania somnifera, are described. A synthetic method of making an indolealkylamino-withasteroid compound is provided. In vitro acetyl cholinesterase inhibitory activity and methods for treatment of dementia and dementia-related disorders, such as Alzheimer's disease, and anxiety and depressive disorders in mammals are demonstrated with these novel compositions.

Abstract: The present invention features novel withanolides, as well as analogs and salts thereof, for use in the treatment of proliferative disease, cardiovascular disease, neurodegenerative disease and inflammatory disease.

Abstract: New aminooxime derivatives at position 3 of 2- and/or 4-substituted androstanes and androstenes, processes for their preparation, and to pharmaceutical compositions containing them for the treatment of cardiovascular disorders, such as heart failure and hypertension. In particular compounds having the general formula (I) are described, where the radicals have the meanings described in detail in the application.

Abstract: Novel withanolide chemical genetic probes identify the in vivo binding target of withaferin A, which is the intermediate filament type III protein vimentin. In addition, a withanolide-based small molecule screening method screens drug candidates that target intermediate filament type III proteins. The method includes introducing a tagged linker covalently bonded to the withanolide molecule to form a withanolide probe. Better or alternative small molecule compounds as potential drug candidates can be generated based on their likely affinity for the determined binding site in vimentin. The affinity labeled withanolide can also be used to find intermediate filament-associated proteins using chemical proteomics by extracting proteins from cells that were exposed to withanolide-biotin analog. The withanolide probes can be used to monitor expression of vimentin, in tumor samples or other diseased tissues.

Abstract: A general, efficient, and environmentally friendly method is provided for producing mostly ?-epoxides of ?5-unsaturated steroids using certain ketones as the catalyst along with an oxidizing agent, or by using certain dioxiranes. In another aspect of the invention, a method is provided for producing mostly 5?,6?-epoxides of steroids from ?5-unsaturated steroids having a substituent at the 3?-position by an epoxidation reaction using a ketone along with an oxidizing agent under conditions effective to generate epoxides, or using a dioxirane under conditions effective to generate epoxides. A whole range of ?5-unsaturated steroids, bearing different functional groups such as hydroxy, carbonyl, acetyl or ketal group as well as different side chains, were conveniently converted to the corresponding synthetically and biologically interesting 5?,6?-epoxides with excellent ?-selectivities and high yields.

Abstract: A general, efficient, and environmentally friendly method is provided for producing mostly &bgr;-epoxides of &Dgr;5-unsaturated steroids using certain ketones as the catalyst along with an oxidizing agent, or by using certain dioxiranes. In another aspect of the invention, a method is provided for producing mostly 5&bgr;,6&bgr;-epoxides of steroids from &Dgr;5-unsaturated steroids having a substituent at the 3&agr;-position by an epoxidation reaction using a ketone along with an oxidizing agent under conditions effective to generate epoxides, or using a dioxirane under conditions effective to generate epoxides. A whole range of &Dgr;5-unsaturated steroids, bearing different functional groups such as hydroxy, carbonyl, acetyl or ketal group as well as different side chains, were conveniently converted to the corresponding synthetically and biologically interesting 5&bgr;,6&bgr;-epoxides with excellent &bgr;-selectivities and high yields.

Abstract: Withajardins A-D are new class of withanolides isolated from the leaves of Deprea orinocensis and characterized by having a bicyclic C-17.beta. system and hydroxyl group at C-14 and C-17. The bicyclic system consists of a lactone and a homocyclic ring with six carbon atoms unlike the acnistins which have a five-membered homocyclic ring. The two classes of compounds were differentiated and their structures were identified by a series of HMQC, HMBC and finally X-ray diffraction experiments. Withajardins and acnistins would seem to evolve along quite dissimilar biosynthetic pathways although both types of compound show a marked immunosupressive effect on in vitro cultures of human lymphocytes.