Evaluation of di-sansalvamide A derivatives: synthesis, structure-activity relationship, and mechanism of action.
Described is the SAR of 18 di-sansalvamide A derivatives and the mechanism of action of the most potent compound. We show that this scaffold is a promising lead in the development of novel cancer therapeutics because it is cytotoxic at nanomolar potency, inhibits a well-established oncogenic target (Hsp90), and does not share structural motifs with current drugs on the market.
Alexander
Leslie D
LD
Department of Chemistry and Biochemistry, San Diego State University, San Diego, CA 92182-1030, USA.
Sellers
Robert P
RP
Davis
Melinda R
MR
Ardi
Veronica C
VC
Johnson
Victoria A
VA
Vasko
Robert C
RC
McAlpine
Shelli R
SR
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D047630:Depsipeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016503:Drug Delivery Systems; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006367:HeLa Cells; D006801:Humans; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D047630:Depsipeptides; D018841:HSP90 Heat-Shock Proteins; C119376:sansalvamide A