Keywords
hMAO inhibitors
Caco-2 permeability
Human liver microsomal metabolic stability
How to Cite
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=0.110.01M and Ki=0.060.002 M 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.References
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