Design, synthesis, and evaluation of a radicicol and geldanamycin chimera, radamide.
A chimera composed of the natural products radicicol and geldanamycin has been prepared through an amide linkage connecting the resorcinol moiety of radicicol to the quinone ring of geldanamycin. The inhibitory activity of these compounds was determined by their ability to inhibit Hsp90's inherent ATPase activity along with degradation of the Hsp90 client protein, HER-2 in MCF-7 breast cancer cells. [reaction: see text]
Clevenger
Randell C
RC
Department of Medicinal Chemistry and The Center for Protein Structure and Function, The University of Kansas, 1251 Wescoe Hall Drive, Malott 4070, Lawrence, KS 66045-7562, USA.
Blagg
Brian S J
BS
D000083:Acetanilides / Q000737:chemistry / Q000494:pharmacology*; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology*; D016227:Benzoquinones; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D015195:Drug Design; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D047029:Lactams, Macrocyclic; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D018942:Macrolides; D011809:Quinones / Q000737:chemistry / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000083:Acetanilides; D000251:Adenosine Triphosphatases; D000970:Antineoplastic Agents; D001565:Benzoates; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D007783:Lactones; D018942:Macrolides; D011809:Quinones; D018719:Erb-b2 Receptor Tyrosine Kinases; C540759:radamide; C035359:monorden; C001277:geldanamycin