Isoquinoline alkaloids as prolyl oligopeptidase inhibitors

Prolyl oligopeptidase is a cytosolic serine peptidase that hydrolyses proline-containing peptides at the carboxy terminus of proline residues. It has been associated with schizophrenia, bipolar affective disorder, and related neuropsychiatric disorders and therefore may have important clinical implications. Thirty-one isoquinoline alkaloids of various structural types, previously isolated in our laboratory, were screened for their ability to inhibit prolyl oligopeptidase. Promising results have been showed by alkaloids californidine (IC50 = 55.6 ± 3.5 μM), dihydrosanquinarine (IC50 = 99.1 ± 7.6 μM), corypalmine (IC50 = 128.0 ± 10.5 μM) and N-methyllaurotetanine (IC50 = 135.0 ± 11.7 μM).

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