Synthesis and Structure–Activity Relationship of Palmatine Derivatives as a Novel Class of Antibacterial Agents against Helicobacter pylori

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 6; p. 1352
• Main Authors: Fan, Tianyun, Guo, Xixi, Zeng, Qingxuan, Wei, Wei, You, Xuefu, Pang, Jing, Wang, Yanxiang, Song, Danqing
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.03.2020; MDPI
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Bacteria; Berberine Alkaloids - chemistry; Berberine Alkaloids - pharmacology; Binding sites; Drug dosages; FDA approval; Gram-negative bacteria; helicobacter pylori; Helicobacter pylori - drug effects; Male; Mice; Microbial Sensitivity Tests; Molecular Docking Simulation; palmatine; Structure-Activity Relationship; synthesis; Toxicity Tests, Acute; Ulcers; urease; Urease - metabolism; synthesis; structure–activity relationship; palmatine; Helicobacter pylori; urease
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25061352

Taking palmatine (PMT) as the lead, 20 new PMT derivatives were synthesized and examined for their antibacterial activities against six tested metronidazole (MTZ)-resistant Helicobacter pylori (H. pylori) strains. The structure–activity relationship (SAR) indicated that the introduction of a suitable secondary amine substituent at the 9-position might be beneficial for potency. Among them, compound 1c exhibited the most potent activities against MTZ-resistant strains, with minimum inhibitory concentration (MIC) values of 4–16 μg/mL, better than that of the lead. It also exhibited a good safety profile with a half-lethal dose (LD50) of over 1000 mg/kg. Meanwhile, 1c might exert its antimicrobial activity through targeting H. pylori urease. These results suggested that PMT derivatives might be a new family of anti-H. pylori components.