Quaternary benzo[c]phenanthridine alkaloids as inhibitors of dipeptidyl peptidase IV-like activity baring enzymes in human blood plasma and glioma cell lines.
Quaternary benzo[c]phenanthridine alkaloids (QBA), fagaronine (FA), sanguinarine (SA), chelerythrine (CHE) and the QBA extract from Macleya cordata (EX) exerted differential inhibitory effect on the hydrolytic activity of particular dipeptidyl peptidase (DPP)-like enzyme isolated from human blood plasma and from human and rat glioma cell lines. The low-MW form of DPP-IV-like enzyme activity, corresponding most probably to DPP-8, observed only in glioma cells but not in human plasma, was inhibited preferentially by SA, CHE and EX, and only slightly by FA. The alkaloid inhibitory effect was concentration-dependent in the range 25-150 mM and directly pH-related. In addition, a subtle but consistent inhibition of the intermediate-MW form of DPP-IV-like enzyme activity, ascribed to DPP-IV/CD26, observed only in human plasma and of the attractin (high-MW form of DPP-IV-like enzyme activity, expressed in U87 glioma cells) by the studied alkaloids was observed. We conclude that some of the QBA biological effects could be determined by tissue and cell type specific dipeptidyl peptidase IV-like molecules expression pattern.
Sedo
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A
Institute of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacký University, Olomouc, Czech Republic. vilim@tunw.upol.cz.
Malík
R
R
Vicar
J
J
Simánek
V
V
Ulrichová
J
J
D000470:Alkaloids / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D053119:Benzophenanthridines; D045744:Cell Line, Tumor / Q000201:enzymology; D002850:Chromatography, Gel / Q000379:methods; D018819:Dipeptidyl Peptidase 4 / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005910:Glioma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007546:Isoquinolines; D028101:Papaveraceae / Q000737:chemistry; D010617:Phenanthridines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013053:Spectrophotometry / Q000379:methods
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010617:Phenanthridines; C002066:fagaronine; C005705:sanguinarine; C016299:chelerythrine; D018819:Dipeptidyl Peptidase 4