RESUMEN
The search for lipoxygenase (LOX) inhibitors has been carried out for decades due to its importance in inflammatory diseases. In the present study, it was observed that the methanolic extract of Cuminum cyminum L. inhibited LOX activity. Activity-guided screening of the C. cyminum crude extracts helped the identification and isolation of cuminaldehyde as a 15-LOX inhibitor. The enzyme kinetics analysis suggested cuminaldehyde to be a competitive inhibitor and the IC 50 value derived from LB plots is 1,370 µM. Binding constants of cuminaldehyde on LOX was deduced by isothermal titration calorimetry. The combined thermodynamics and molecular modeling analyses suggested cuminaldehyde as a competitive LOX inhibitor. It is proposed from the present study that the coordinate bond between the Fe(2+) atom in the active site of the enzyme and the cuminaldehyde may be responsible for the enzyme inhibition. The study suggests that cuminaldehyde may be acting as an anti-inflammatory compound and may be therefore included in the category of leads for developing dual COX-LOX inhibitors as non-steroidal anti-inflammatory drugs (NSAIDs).
