Bioorganic & Medicinal Chemistry 2008-07-01

Synthetic and pharmacological studies on new simplified analogues of the potent actin-targeting Jaspamide.

Stefania Terracciano, Ines Bruno, Elisabetta D'Amico, Giuseppe Bifulco, Angela Zampella, Valentina Sepe, Charles D Smith, Raffaele Riccio

Index: Bioorg. Med. Chem. 16 , 6580-8, (2008)

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Abstract

In the recent years, we focused our attention on the cyclodepsipeptide Jaspamide 1, an interesting marine metabolite, possessing a potent inhibitory activity against breast and prostate cancer, as a consequence of its ability to disrupt actin cytoskeleton dynamics. Although its biological profile has been well determined, many mechanistic details are still missing in terms of molecular target identification. For this reason, we decided to synthetically modify the natural metabolite, obtaining small arrays of unnatural variants useful to illuminate the structural requirements essential for the activity. Here, we report the synthesis of seven new Jaspamide analogues 2-8, containing, as the parent compound, a beta-amino acid in the cyclopeptide backbone. Their biological profile is also described.