Synthesis and biological evaluation of arylated novobiocin analogs as Hsp90 inhibitors.
Novobiocin analogs lacking labile glycosidic ether have been designed, synthesized and evaluated for Hsp90 inhibitory activity. Replacement of the synthetically complex noviose sugar with simple aromatic side chains produced analogs that maintain moderate cytotoxic activity against MCF7 and SkBR3 breast cancer cell-lines. Rationale for the preparation of des-noviose novobiocin analogs in addition to their synthesis and biological evaluation are presented herein.
Department of Medicinal Chemistry, The University of Kansas, Lawrence, KS 66045-7563, USA.
Bhaskar Reddy
BR
Kusuma
Adam S
AS
Duerfeldt
Brian S J
BS
Blagg
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D015394:Molecular Structure; D009675:Novobiocin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D009675:Novobiocin