Synthesis and cytotoxicity of a new class of potent decapeptide macrocycles.
Described are the syntheses of five decapeptides that are C-2-symmetrical derivatives of the natural product pentapeptide sansalvamide A. Derivatives were made using a succinct convergent synthesis. These analogues share no structural homology to current cancer drugs, are cytotoxic at levels on par with existing drugs treating cancers, and demonstrate selectivity for drug-resistant pancreatic cancer cell lines over noncancerous cell lines. These molecules are excellent chemotherapeutic leads in the search for new anticancer agents.
Davis
Melinda R
MR
Department of Chemistry, Molecular Biology Institute, and Center for Applied and Experimental Genomics, 5500 Campanile Road, 208 CSL, San Diego State University, San Diego, California 92182-1030, USA.
Styers
Thomas J
TJ
Rodriguez
Rodrigo A
RA
Pan
Po-Shen
PS
Vasko
Robert C
RC
McAlpine
Shelli R
SR
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D047630:Depsipeptides; C119376:sansalvamide A