New inhibitors of the thioredoxin-thioredoxin reductase system based on a naphthoquinone spiroketal natural product lead.
Natural products of the naphthoquinone spiroketal structural type served as lead structures for the development of novel inhibitors of the thioredoxin-thioredoxin reductase redox system. The most potent compound in this series inhibited thioredoxin with an IC(50) of 350 nM, and many derivatives showed low micromolar activities for growth inhibition against two breast cancer cell lines.
Wipf
P
P
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA. pwipf@pitt.edu
Hopkins
T D
TD
Jung
J K
JK
Rodriguez
S
S
Birmingham
A
A
Southwick
E C
EC
Lazo
J S
JS
Powis
G
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004146:Dioxanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009281:Naphthalenes; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors*; D013879:Thioredoxins / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004146:Dioxanes; D004852:Epoxy Compounds; D009281:Naphthalenes; D009285:Naphthoquinones; D013141:Spiro Compounds; C089783:diepoxin sigma; C422643:palmarumycin CP(1); D013879:Thioredoxins; D013880:Thioredoxin-Disulfide Reductase