Synthesis of Sansalvamide A derivatives and their cytotoxicity in the MSS colon cancer cell line HT-29 |
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Authors: | Styers Thomas J Kekec Ahmet Rodriguez Rodrigo Brown Joseph D Cajica Julia Pan Po-Shen Parry Emily Carroll Chris L Medina Irene Corral Ricardo Lapera Stephanie Otrubova Katerina Pan Chung-Mao McGuire Kathleen L McAlpine Shelli R |
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Affiliation: | Department of Chemistry and Biochemistry, San Diego State University, CA 92182-1030, USA. |
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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. |
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