title: Synthesis of Sansalvamide A derivatives and their cytotoxicity in the MSS colon cancer cell line HT-29.
abstract: We report the synthesis of thirty-six Sansalvamide A derivatives, and their biological activity against colon cancer HT-29 cell line, a microsatellite stable (MSS) colon cancer cell-line. The thirty-six compounds can be divided into three subsets, where the first subset of compounds contains L-amino acids, the second subset contains D-amino acids, and the third subset contains both D- and L-amino acids. Five compounds exhibited excellent inhibitory activity (>75% inhibition). The structure-activity relationship (SAR) of the compounds established that a single D-amino acid in position 2 or 3 gave up to a 10-fold improved cytotoxicity over Sansalvamide A peptide. This work highlights the importance of residues 2 and 3 and the role of D-amino acids in the extraordinary SAR for this compound class.
authors.affiliation: Department of Chemistry and Biochemistry, San Diego State University, CA 92182-1030, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Styers
authors.forename: Ahmet
authors.initials: A
authors.lastname: Kekec
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Rodriguez
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Brown
authors.forename: Julia
authors.initials: J
authors.lastname: Cajica
authors.forename: Po-Shen
authors.initials: PS
authors.lastname: Pan
authors.forename: Emily
authors.initials: E
authors.lastname: Parry
authors.forename: Chris L
authors.initials: CL
authors.lastname: Carroll
authors.forename: Irene
authors.initials: I
authors.lastname: Medina
authors.forename: Ricardo
authors.initials: R
authors.lastname: Corral
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lapera
authors.forename: Katerina
authors.initials: K
authors.lastname: Otrubova
authors.forename: Chung-Mao
authors.initials: CM
authors.lastname: Pan
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: McGuire
authors.forename: Shelli R
authors.initials: SR
authors.lastname: McAlpine
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000473:pathology; D047630:Depsipeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D019073:HT29 Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D047630:Depsipeptides; C119376:sansalvamide A; D013936:Thymidine