Synthesis and Structure–Activity Relationship of Palmatine Derivatives as a Novel Class of Antibacterial Agents against Helicobacter pylori
| Autor: | Jing Pang, Dan-Qing Song, Qingxuan Zeng, Xuefu You, Yan-Xiang Wang, Wei Wei, Xi-Xi Guo, Tian-Yun Fan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
structure–activity relationship
Urease synthesis Pharmaceutical Science Pharmacology Analytical Chemistry lcsh:QD241-441 03 medical and health sciences chemistry.chemical_compound Minimum inhibitory concentration 0302 clinical medicine lcsh:Organic chemistry Drug Discovery palmatine medicine Structure–activity relationship Potency Physical and Theoretical Chemistry 030304 developmental biology urease 0303 health sciences biology Organic Chemistry Helicobacter pylori Palmatine biology.organism_classification Antimicrobial bacterial infections and mycoses Metronidazole chemistry Chemistry (miscellaneous) 030220 oncology & carcinogenesis biology.protein Molecular Medicine medicine.drug |
| Zdroj: | Molecules Volume 25 Issue 6 Molecules, Vol 25, Iss 6, p 1352 (2020) |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules25061352 |
| Popis: | 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&ndash 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&ndash 16 &mu g/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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|