Towards the anti-fibrillogenic activity of phthalocyanines with out-of-plane ligands: correlation with self-association proneness

V. B. Kovalska, M. Yu. Losytskyy, S. V. Chernii, V. Ya. Chernii, I. M. Tretyakova, S. M. Yarmoluk, S. V. Volkov
2013 Biopolymers and Cell  
Aim. The activity of five hafnium phthalocyanines containing out-of-plane ligands as inhibitors of reaction of insulin fibril formation is studied and correlation between their inhibitory properties and tendency to selfassociation is discussed. Methods. Fluorescence and absorption spectroscopy. Results. For the complexes with weak proneness to self-association PcHfDbm 2 , PcHfPyr 2 , and PcHfBtfa 2 the values of inhibitory activity were estimated as 60-73 %. For phthalocyanines with the
more » ... es with the pronounced tendency to self-association PcHfPiromelit and PcHfCl 2 the noticeably higher inhibitory activity values (about 95 %) were shown. In the presence of native or fibrilar insulin the destruction of self-associates of metal complex occurs in buffer pH 7.9, Besides upon the conditions of insulin fibrillization reaction (0.1 M HCl) phthalocyanines exist predominantly as monomers. Conclusions. The phthalocyanines with out-of-plane ligands with higher tendency to self-association have shown higher inhibitory activity in the insulin fibril formation comparing with the poorly aggregated metal complexes. At the same time low-order self-associates are not involved directly in th] mechanism of inhibition of insulin fibrillization and the phthalocyanines bind with protein in monomeric form. Tendency of phthalocyanines to self-association in aqueous media seems to be an «indicator» of their proneness to stack with protein aromatic amino-acids and thus of anti-fibrilogenic properties.
doi:10.7124/bc.00083c fatcat:5t7uuxgidfg3fezshkciaibaj4