Exploring the binding interaction between triazoles and bromelain by spectroscopic and molecular docking techniques

The study of interaction between small molecule and biomacromolecule is highly important in the field of research in biochemistry, pharmaceutical and medicinal chemistry. Here bromelain, a pineapple-stem enzyme is taken as the biomacromolecule and its binding interaction with triazole-based organic molecules are investigated by steady state absorption and emission spectroscopy. The experimental results are supplemented by molecular docking. The triazoles are designed by mimicking the structure of Vorinostat which a bioactive compound. In this paper, we have explored the biophysical interaction of three triazole based ligands with cysteine protease enzyme bromelain for the very first time using steady-state fluorescence and temperature variation experimentally, also compared them with two of our previously published triazoles molecules (SSAM 1 as C-1 and SAM 1 as C-5). The triazole moiety in these compounds are found to be involved in pi-interactions and hydrogen bonding with the amino acid residues present in bromelain and provides stability to the bromelain-small molecule complexes. At lower temperature the binding of these compounds with bromelain becomes relatively more spontaneous. The study shows that the presence of triazole at terminal end in the molecule can make them an inhibitor of bromelain's proteolytic acitivity. But the presence of triazole at cap region provides better binding interaction of the ligand with bromelain under physiological condition.