Structural modeling and simulation studies of human cyclooxygenase (COX) isozymes with selected terpenes:...

Area of Science:

• Biochemistry
• Pharmacology
• Computational Chemistry

Background:

• Cyclooxygenase-1 (COX-1) plays a role in human health and diseases, including cancer.
• Developing safe and selective COX-1 inhibitors is a therapeutic goal.
• Terpenoids are natural compounds with potential medicinal properties.

Purpose of the Study:

• To investigate the potential of terpenoids as selective inhibitors of human COX-1 and COX-2 isozymes.
• To identify specific terpenoids with potent COX-1 inhibitory activity.
• To compare the inhibitory efficacy of terpenoids with known drugs.

Main Methods:

• In silico modeling of human COX-1 and COX-2 isozymes.
• Molecular docking simulations to assess the binding affinities of terpenoids.
• Evaluation of binding energies and inhibition constants (Ki).

Main Results:

• All 10 tested terpenoids demonstrated greater potency as COX-1 inhibitors compared to COX-2 inhibitors.
• Oleanolic acid emerged as the most potent inhibitor of both COX-1 and COX-2.
• Beta-carotene was identified as the most selective COX-1 inhibitor among the tested terpenoids.
• Ibuprofen and aspirin showed preferential inhibition of COX-1 and COX-2, respectively.

Conclusions:

• Terpenoids, particularly oleanolic acid and beta-carotene, represent promising candidates for developing selective COX-1 inhibitors.
• These findings support the exploration of terpenoids as novel therapeutic agents for COX-1-related diseases, including cancer.
• In silico methods provide a valuable approach for screening natural compounds as drug candidates.