Zn-Phenanthroline-Dicarboxylate Complex: A Dual Inhibitor of COX-2 and 5-LOX Enzymes

A series of new phenanthroline-based metal complexes, coordination polymers are synthesized using 1,10-phenanthroline 2,9-dicarboxylate (PDA) and different metal salts including tin (R-1 to R-3), manganese (R-4), ruthenium (R-5), and zinc (R-6) respectively. The inhibitory activities of synthesized coordination compounds are evaluated towards COX-2 (cyclooxygenase-2) and 5-LOX (5-lipoxygenase) enzymes. Among all the metal-organic coordination complexes, Zn-PDA (R-6) shows most prominent inhibitory activity than other systems with the IC50 value of 0.0524 mu g/mL and 0.834 mu g/mL for both COX-2 and 5-LOX enzymes, respectively. The synthesized systems were also evaluated for their activity against COX-1 and standard COX-2 inhibitors viz. Rofecoxib and Aspirin. The rationale for R-6 being the most potent metal complex for dual COX-2 and 5-LOX inhibition is demonstrated using docking studies. A series of Metal-phenanthroline-carboxylate- coordination compounds (R1 to R6) were designed and synthesized. Among all the metal complexes tested for inhibitory activities for COX-2 and 5-LOX enzymes, the activities of R-1 and R-6 were found to be most potent. image