Synthesis and biological activity of prodrug inhibitors of the thioredoxin-thioredoxin reductase system.
A series of palmarumycin prodrugs and water-soluble analogs has been synthesized and assayed for inhibition of the thioredoxin-thioredoxin reductase system. Increased aqueous solubility led to an improved in vivo activity profile.
Wipf
Peter
P
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA. pwipf@pitt.edu
Lynch
Stephen M
SM
Powis
Garth
G
Birmingham
Anne
A
Englund
Erikah E
EE
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D012995:Solubility; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors*; D013879:Thioredoxins / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D009281:Naphthalenes; D011355:Prodrugs; D013141:Spiro Compounds; C462879:palmarumycin C2; D013879:Thioredoxins; D013880:Thioredoxin-Disulfide Reductase