Synthesis, structural characterization, and evaluation of new peptidomimetic Schiff bases as potential antithrombotic agents.

New Schiff bases functionalized with amide and phenolic groups synthesized by the condensation of 2-hydroxybenzaldehyde and 2-hydroxyacetophenone with amino acid amides which in turn were prepared in two steps from N-Boc-amino acids and homoveraltrylamine through intermediate compounds N-Boc-amino acids amides. The compounds were characterized by elemental analysis, FT-IR, UV-Vis, and NMR spectroscopy. The crystal structures of three Schiff bases were determined by single crystal X-ray diffraction. There exists O-H $\cdots$ N, N-H $\cdots$ O, and C-H $\cdots$ O types of hydrogen bonds and C-H $\cdots \pi$ secondary bonding interactions in these crystalline solids. The Schiff bases have been screened for anticoagulant and antiplatelet aggregation activities. All the compounds showed procoagulant activity which shortens the clotting time of citrated human plasma in both platelet-rich plasma and platelet-poor plasma except the derivatives of L-methionine which showed anticoagulant activity by prolonging the clotting time. In addition, the compounds derived from benzyl cysteine and phenylalanine showed adenosine diphosphate induced antiplatelet aggregation activity, whereas others did not show any role. Moreover, all these compounds revealed non-hemolytic activity with red blood cells.

Graphical abstract:

Supplementary information: The online version contains supplementary material available at 10.1007/s00706-022-02936-6.