title: Neuraminidase inhibitory activities of quaternary isoquinoline alkaloids from Corydalis turtschaninovii rhizome.
abstract: Clostridium perfringens is a Gram-positive spore-forming bacterium that causes food poisoning. The neuraminidase (NA) protein of C. perfringens plays a pivotal role in bacterial proliferation and is considered a novel antibacterial drug target. Based on screens for novel NA inhibitors, a 95% EtOH extract of Corydalis turtschaninovii rhizome showed NA inhibitory activity (68% at 30 μg/ml), which resulted in the isolation of 10 isoquinoline alkaloids; namely, palmatine (1), berberine (2), coptisine (3), pseudodehydrocorydaline (4), jatrorrhizine (5), dehydrocorybulbine (6), pseudocoptisine (7), glaucine (8), corydaline (9) and tetrahydrocoptisine (10). Interestingly, seven quaternary isoquinoline alkaloids 1-7 (IC50 = 12.8 ± 1.5 to 65.2 ± 4.5 μM) showed stronger NA inhibitory activity than the tertiary alkaloids 8-10. In addition, highly active compounds 1 and 2 showed reversible non-competitive behavior based on a kinetic study. Molecular docking simulations using the Autodock 4.2 software increased our understanding of receptor-ligand binding of these compounds. In addition, we demonstrated that compounds 1 and 2 suppressed bacterial growth.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Jang Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Infection Control Material Research Center and AI Control Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 580-185, Republic of Korea.
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Ryu
authors.affiliation: Infection Control Material Research Center and AI Control Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 580-185, Republic of Korea. Electronic address: wslee@kribb.re.kr.
authors.forename: Woo Song
authors.initials: WS
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: yhk@cnu.ac.kr.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D003015:Clostridium Infections / Q000188:drug therapy; D003016:Clostridium perfringens / Q000187:drug effects / Q000201:enzymology*; D031311:Corydalis / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D027343:Rhizome / Q000737:chemistry
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D009439:Neuraminidase
keywords: Bacterial neuraminidase; Corydalis turtschaninovii; Fumariaceae; Isoquinoline alkaloids; Non-competitive inhibition