Synthesis and antiproliferative activity of culicinin D analogues containing simplified AHMOD-based residues.

Eur J Med Chem

School of Chemical Sciences, The University of Auckland, 23 Symonds St, Auckland, 1010, New Zealand; The Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland, 1010, New Zealand; School of Biological Sciences, The University of Auckland, 3A Symonds St, Auckland, 1010, New Zealand. Electronic address:

Published: September 2019

Culicinin D is a 10 amino acid peptaibol containing a rare and synthetically challenging (2S,4S,6R)-AHMOD residue, that exhibits potent antiproliferative activity against MDA-MB-468 cells. An SAR study focusing on replacement of the AHMOD residue was undertaken, culminating in the revelation that a 6-hydroxy or 6-keto substituent was essential to retain potent low nanomolar antiproliferative activity.

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http://dx.doi.org/10.1016/j.ejmech.2019.05.052DOI Listing

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