T. V. Osadchuk¹, V. K. Kibirev^1,2, O. V. Shybyryn¹, A. V. Semyroz¹,
Ye. S. Velihina¹, Е. R. Abdurakhmanova¹, V. S. Brovarets¹

¹V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry,
National Academy of Sciences of Ukraine, Kyiv;
e-mail: brovarets@bpci.kiev.ua;
²Palladin Institute of Biochemistry, National Academy
of Sciences of Ukraine, Kyiv

Received: 22 February 2019; Accepted: 17 May 2019

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 ¹H, ³¹P 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-yl-triphenylphosphonium salts may be useful for developing new more potent and selective inhibitors of furin.