Ukr.Biochem.J. 2019; Volume 91, Issue 4, Jul-Aug, pp. 5-16

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

T. V. Osadchuk1, V. K. Kibirev1,2, 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 (Ki = 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.

Keywords: , , , ,


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