Resumo

RODRIGUEZ, Rodrigo A. et al. Structure-activity of Sansalvamide A Derivatives and their Apoptotic Activity in the Pancreatic Cancer Cell Line PL-45. J. Mex. Chem. Soc [online]. 2008, vol.52, n.3, pp.201-211. ISSN 1870-249X.

We report the structure-activity relationship (SAR) of forty Sansalvamide A (San A) derivatives against human pancreatic ductal adenicarcinoma cell line PL-45. Our comprehensive evaluation of these compounds utilizes: cytotoxicity based SAR, molecular modeling, and ApoAlert Annexin V apoptosis detection to evaluate these potent compounds. Compared to current pancreatic cancer drugs, these San A analogs are structurally unique, and are potentially cytotoxic. Our comprehensive studies including molecular modeling show that a single N-methyl, a single D-amino acid (D-aa) or a single N -methyl D-aa appears to be critical for presenting the active conformation of San A peptide derivates to its biological target, and show that the San A peptide derivative 8 has the ability to selectively induce apoptosis. Thus, showing that this class of compounds are promising chemotherapeutic agents that will eliminate cells in an orderly manner without eliciting an undesired immune response.

Palavras-chave : structure-activity relationship; Sansalvamide A; human pancreatic adenicarcinoma; molecular modeling; apoptosis.

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