Potent antitumor agents: Sansalvamide A derivatives

ORGN 151

Rodrigo A. Rodriguez, nakbetanu124@yahoo.com1, Katerina Otrubova1, Thomas J. Styers, tstyers209@yahoo.com1, Po-Shen Pan, robertsdsu2003@yahoo.com.tw1, Julia Cajica1, Emily Parry1, Ahmet Kekec, ahmetkekec23@yahoo.com1, Kathleen McGuire2, and Shelli McAlpine1. (1) Department of Chemistry and Biochemistry, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182, (2) Department of Biology, San Diego State University
Described is the discovery of an extraordinary structure-activity relationship between forty-five Sansalvamide A compounds and their potency against colon cancer cell line HT-29. Eleven Sansalvamide A derivatives are significantly more potent than Sansalvamide A peptide. One compound, is ten-fold more potent than Sansalvamide A (IC50=4.5µg/ml versus San A peptide IC50 = 45µg/ml). We present data demonstrating that Sansalvamide A derivatives that contain an exchange of one L-amino acid with a structurally similar D-amino acid in position 2 or position 3 exhibit excellent “drug-like” potency against colon cancer.