Heterocyclic substituted non-protein amino acids as inhibitors of Clostridium histolyticum collagenase

Abstract

Optically active non-protein α-amino acids have been screened for their ability to interact with collagenase of Clostridium histolyticum. Both structure-based drug design approach (modeling) and that of determining enzyme activity in the presence of amino acids have been used to identify low molecular weight inhibitors of collagenase. According to the docking analysis, a number of non-protein amino acids have demonstrated ability to form bounds with collagenase. Following the docking analysis, enzyme activity has been determined in the presence of investigated amino acids. The results have indicated that (S)-β-[4-allyl-3-butyl-5-thioxo-1,2,4-triazol-1-yl]-α-alanine, (S)-β-[4-allyl-3-(pyridin-4’-yl)-5-thioxo-1,2,4-triazol-1-yl]-α-alanine and (S)-β-[4-allyl-3-(pyridin-3’-yl)-5-thioxo-1,2,4-triazol-1-yl]-α-alanine inhibit collagenase activity.