Abstract
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 mu M), dihydrosanquinarine (IC50 = 99.1 +/- 7.6 mu M), cotypalmine (IC50 = 128.0 +/- 10.5 mu M) and N-methyllaurotetanine (IC50 = 135.0 +/- 11.7 mu M).