title: Quaternary benzo[c]phenanthridine alkaloids as inhibitors of aminopeptidase N and dipeptidyl peptidase IV.
abstract: Chelerythrine, sanguinarine and an alkaloid extract from Macleaya cordata--sanguiritrin--were found to be inhibitors of aminopeptidase A and dipeptidyl peptidase IV, while fagaronine inhibited dipeptidyl peptidase IV only. At 50 microM, chelerythrine, sanguinarine and sanguiritrin inhibited aminopeptidase N by 82%, 82%, 88%, DPP IV by 38%, 62%, 57%, and fagaronine by 34%, respectively. When bovine serum albumin (500 microg/mL) was added, the inhibition of both proteases by quaternary benzo[c]phenanthridine alkaloids (QBA) (50 microM) was significantly diminished. Strong interaction of chelerythrine and sanguinarine with bovine and human serum albumin was proved by electrophoretic determination of their respective conditional binding constants.
authors.affiliation: Joint Laboratory of Cancer Cell Biology of the 1st Faculty of Medicine, Charles University and Institute of Physiology, Academy of Sciences, 121 08 Prague, Czech Republic.
authors.forename: Aleksi
authors.initials: A
authors.lastname: Sedo
authors.forename: Kvetoslava
authors.initials: K
authors.lastname: Vlasicová
authors.forename: Petr
authors.initials: P
authors.lastname: Barták
authors.forename: Radim
authors.initials: R
authors.lastname: Vespalec
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Vicar
authors.forename: Vilim
authors.initials: V
authors.lastname: Simánek
authors.forename: Jitka
authors.initials: J
authors.lastname: Ulrichová
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D053119:Benzophenanthridines; D018826:CD13 Antigens / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002417:Cattle; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines; D015394:Molecular Structure; D028101:Papaveraceae; D010617:Phenanthridines / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D012709:Serum Albumin / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010617:Phenanthridines; D010936:Plant Extracts; D012709:Serum Albumin; C002066:fagaronine; C005705:sanguinarine; C016299:chelerythrine; D011493:Protein Kinase C; D018826:CD13 Antigens; D018819:Dipeptidyl Peptidase 4