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

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Pharmaceutical Science

Background:

• Biomacromolecule-small molecule interactions are crucial in drug discovery.
• Bromelain, a cysteine protease from pineapple, serves as a model biomacromolecule.
• Triazole-based compounds are explored for their potential bioactivity.

Purpose of the Study:

• To investigate the biophysical interactions between bromelain and novel triazole-based ligands.
• To understand how structural modifications of triazole ligands affect binding affinity and stability with bromelain.
• To evaluate the potential of these triazole compounds as inhibitors of bromelain's proteolytic activity.

Main Methods:

• Steady-state absorption and emission spectroscopy were employed to study binding interactions.
• Temperature variation experiments were conducted to analyze thermodynamic parameters.
• Molecular docking simulations supplemented experimental findings.

Main Results:

• Triazole ligands form pi-interactions and hydrogen bonds with bromelain residues, enhancing complex stability.
• Lower temperatures promote more spontaneous binding of the ligands to bromelain.
• Ligand structure influences binding: terminal triazoles may inhibit activity, while cap-region triazoles show better binding under physiological conditions.

Conclusions:

• Triazole-based compounds exhibit significant binding interactions with bromelain.
• The position of the triazole moiety critically affects the binding efficacy and potential inhibitory activity.
• These findings offer insights into designing effective bromelain inhibitors for pharmaceutical applications.