Monoamine oxidase-A inhibitory activity of novel Curcumin analogues

Abstract

Curcumin has been known for its antidepressant activity, but its use has been restricted due to its poor pharmacokinetic properties . In an effort to enhance its permeability and metabolic stability , a series of four novel curcumin analogues (5a - ­‐5d) were synthesized. They were tested for their hMAO inhibitory activity as well as for their permeability and metabolic stability characteristics in in vitro models . The newly synthesized compounds were found to be potent when compared with curcumin and also they are selective and reversible towards hMAO - ­‐A . Compounds 5c and 5d were found to be potent inhibitors of hMAO - ­‐A with Ki values of Ki=0 . 11±0 . 01µM and Ki=0 . 06±0 . 002 µM and with selectivity index of SIMAO - ­‐ A=802 . 36 and SIMAO - ­‐ A=507 . 33 , respectively . A slight enhancement in metabolic stability is achieved through the chemical modification .