title: Viridin analogs derived from steroidal building blocks.
abstract: Naturally occurring furanosteroids such as viridin and wortmannin have long been known as potent inhibitors of the lipid kinase PI-3K. We have been interested in directly accessing analogs of these complex natural products from abundant steroid feedstock materials. In this communication, we describe the synthesis of viridin/wortmannin hybrid molecules from readily available building blocks that function as PI-3K inhibitors and maintain their electrophilic properties. The compounds also show anti-proliferative effects against a breast cancer line.
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, United States.
authors.forename: Kishore
authors.initials: K
authors.lastname: Viswanathan
authors.forename: Sophia N
authors.initials: SN
authors.lastname: Ononye
authors.forename: Harold D
authors.initials: HD
authors.lastname: Cooper
authors.forename: M
authors.initials: M
authors.lastname: Kyle Hadden
authors.forename: Amy C
authors.initials: AC
authors.lastname: Anderson
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Wright
mesh_terms: D000730:Androstadienes / Q000737:chemistry; D000736:Androstenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001430:Bacteriocins / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D017434:Protein Structure, Tertiary; D013256:Steroids / Q000737:chemistry*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D000736:Androstenes; D001430:Bacteriocins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D013256:Steroids; D000077191:Wortmannin; C012097:viridin