1,3-Oxazol-4-ylphosphonium salts as new non-peptide inhibitors of furin

Abstract

a series of novel triphenylphosphonium derivatives of 1,3-oxazole containing at c2 and c5-positions electron withdrawing or electron-donating groups were synthesized and characterized by 1 h, 31 P Nmr and Ir spectroscopy, element analysis and chromato-mass spectrometry. These compounds were found to be a new class of non-peptide inhibitors of furin. depending on the chemical structure, they inactivated enzyme at micromolar level by mechanism of competitive, non-competitive or mixed inhibition. evaluation of the synthesized derivatives as furin inhibitors showed that among the triphenylphosphonium salts studied by us, oxazole 12 containing 2,4-dichlorophenyl-in the c2-position and meS-group at c5 is the most active (k i = 1.57 μm) competitive inhibitor of furin. our results provided evidence that chemical modification of 1,3-oxazole-4-yltriphenylphosphonium salts may be useful for developing new more potent and selective inhibitors of furin. k e y w o r d s: furin, inhibitors, 1,3-oxazole derivatives, triphenylphosphonium salts, mechanism of inhibition.