title: Inhibitory effects of furoquinoline alkaloids from Melicope confusa and Dictamnus albus against human phosphodiesterase 5 (hPDE5A) in vitro.
abstract: Eight furoquinoline alkaloids were purified from two plants belonging to the Rutaceae family. Kokusaginine, skimmianine, evolitrine, and confusameline were purified from Melicope confusa, and haplopine, robustine, dictamine, and gamma-fagarine from Dictamnus albus. In this study, the eight furoquinoline alkaloids were examined for inhibitory potency against human phosphodiesterase 5 (hPDE5A) in vitro. DNA encoding the catalytic domain of human PDE5A was amplified from the mRNA of T24 cells by RT-PCR and was fused to GST in an expression vector. GST-tagged PDE5A was then purified by glutathione affinity chromatography and used in inhibition assays. Of the eight alkaloids, gamma-fagarine was the most potent inhibitor of PDE5A, and its single methoxy group at the C-8 position was shown to be critical for inhibitory activity. These results clearly illustrate the relationship between PDE5A inhibition and the methoxy group position in furoquinoline alkaloids.
authors.affiliation: Jung-San Biotechnology Institute, 61 Dukjeul-Ri, Jeongnam-Myun, Whasoung-City, Kyunggi-Do, Korea.
authors.forename: Kung-Woo
authors.initials: KW
authors.lastname: Nam
authors.forename: Kang-Hoon
authors.initials: KH
authors.lastname: Je
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Shin
authors.forename: Sam Sik
authors.initials: SS
authors.lastname: Kang
authors.forename: Woongchon
authors.initials: W
authors.lastname: Mar
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D036905:Dictamnus / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D011804:Quinolines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D027821:Rutaceae / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D004791:Enzyme Inhibitors; D011804:Quinolines; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human