Synthesis of second-generation sansalvamide A derivatives: novel templates as potential antitumor agents.
We report the synthesis of 34 second-generation Sansalvamide A derivatives. San A derivatives have unique anticancer properties and target multiple cancers, including colon, pancreatic, breast, prostate, and melanoma. As novel templates, the derivatives described herein explore the role of stereochemistry, amide bond geometry, transannular hydrogen bonding, and polarity on antitumor potency. Testing the chemotherapeutic activity of these derivatives against multiple cancer cell lines will provide clear structural motifs and identify conformational space that is important for cytotoxicity. The 34 compounds presented are divided into six series, where five series involve the insertion of D-amino acids in conjunction with four structural features at each of the five positions of the macrocycle. The sixth series involves comparison between all L- and all D-amino acid derivatives with N-methyls placed at each position around the macrocyclic core. The four structural features explored in conjunction with D-amino acids include N-methyl amino acids, aromatic amino acids, polar amino acids, and hydrophobic alkyl amino acids.
Rodriguez
Rodrigo A
RA
Department of Chemistry and Biochemistry, San Diego State University, 5500 Campanile Drive, San Diego, California 92182-1030, USA.
Pan
Po-Shen
PS
Pan
Chung-Mao
CM
Ravula
Suchitra
S
Lapera
Stephanie
S
Singh
Erinprit K
EK
Styers
Thomas J
TJ
Brown
Joseph D
JD
Cajica
Julia
J
Parry
Emily
E
Otrubova
Katerina
K
McAlpine
Shelli R
SR
D000596:Amino Acids; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D047630:Depsipeptides / Q000138:chemical synthesis*; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D013237:Stereoisomerism
D000596:Amino Acids; D000970:Antineoplastic Agents; D047630:Depsipeptides; C119376:sansalvamide A