Synthesis and cytotoxicity of a new class of potent decapeptide macrocycles.

Described are the syntheses of five decapeptides that are C-2-symmetrical derivatives of the natural product pentapeptide sansalvamide A. Derivatives were made using a succinct convergent synthesis. These analogues share no structural homology to current cancer drugs, are cytotoxic at levels on par with existing drugs treating cancers, and demonstrate selectivity for drug-resistant pancreatic cancer cell lines over noncancerous cell lines.

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.

Synthesis of Sansalvamide A derivatives and their cytotoxicity in the MSS colon cancer cell line HT-29.

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).

Synthesis and novel structure-activity relationships of potent sansalvamide A derivatives.

Synthesis of twelve Sansalvamide A derivatives and their SAR against colon cancer (HT-29).