Pannorin isolated from marine <i>Penicillium</i> sp. SG-W3: a selective monoamine oxidase A inhibitor

초록

Six compounds were isolated from Penicillium sp. SG-W3, a marine-derived fungus, and their inhibitory activities against target enzymes relating to neurological diseases were evaluated. Compound 1 (pannorin) was a potent and selective monoamine oxidase (MAO)-A inhibitor with a 50% inhibitory concentration (IC50) of 1.734 mu M and a selectivity index (SI) of > 23.07 versus MAO-B, and it showed an efficient antioxidant activity. All compounds showed weak inhibitory activities against acetylcholinesterase, butyrylcholinesterase, and beta-secretase. The inhibition constant (Ki) of 1 for MAO-A was 1.049 +/- 0.030 mu M with competitive inhibition. Molecular docking simulation predicted that compound 1 forms hydrogen bonds with MAO-A, and binds more tightly to MAO-A than to MAO-B (- 25.02 and - 24.06 kcal/mol, respectively). These results suggest that compound 1 is a selective, reversible, and competitive MAO-A inhibitor that can be a therapeutic candidate for treating neurological diseases.

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