Neuraminidase inhibitory activities of quaternary isoquinoline alkaloids from Corydalis turtschaninovii rhizome

• Published in: Bioorganic & medicinal chemistry 2014-11, Vol.22 (21), p.6047-6052
• Main Authors: Kim, Jang Hoon, Ryu, Young Bae, Lee, Woo Song, Kim, Young Ho
• Format: Article
• Language: English
• Subjects: Alkaloids - chemistry; Alkaloids - isolation & purification; Alkaloids - pharmacology; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - isolation & purification; Anti-Bacterial Agents - pharmacology; Bacterial neuraminidase; Clostridium Infections - drug therapy; Clostridium perfringens - drug effects; Clostridium perfringens - enzymology; Corydalis - chemistry; Corydalis turtschaninovii; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Fumariaceae; Humans; Isoquinoline alkaloids; Isoquinolines - chemistry; Isoquinolines - isolation & purification; Isoquinolines - pharmacology; Molecular Docking Simulation; Neuraminidase - antagonists & inhibitors; Neuraminidase - metabolism; Non-competitive inhibition; Rhizome - chemistry
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2014.09.004

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 30μg/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±4.5μM) 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.