AI Article Synopsis
- Thirty new protoberberine derivatives were synthesized to test their effectiveness against Helicobacter pylori, focusing on a compound called 2,3,10-trimethoxy-9-p-methylbenzylaminoprotopalmatine chloride as the lead.
- The most promising derivative, 7c, showed strong anti-bacterial activity against both metronidazole-resistant and susceptible strains, with minimal toxicity and stability in testing conditions.
- The compound 7c is believed to work by targeting HP urease and affecting bacterial membrane permeability, making it a valuable candidate for further development as a treatment for H. pylori infections.
Article Abstract
Thirty protoberberine derivatives, of which twenty five were new, were synthesized and evaluated for their anti-Helicobacter pylori (HP) activities, taking 2,3,10-trimethoxy-9-p-methylbenzylaminoprotopalmatine chloride 1 as the lead. Among them, berberine (BBR) derivative 7c displayed the highest potency against six tested metronidazole (MTZ)-resistant strains and two tested MTZ-susceptible strains with the MIC values of 0.4-1.6 μg/mL with favorable druglike profiles including low toxicity and high stabilities in plasma and artificial gastric fluid. Mechanistic study revealed that 7c might target HP urease with IC value of 0.27 μg/mL against Jack bean urease. Furthermore, 7c might change the permeability of the bacterial membrane and direct interact with HP DNA, which also contribute to its bactericidal activity. Therefore, BBR derivatives constituted a new family of anti-HP candidates, with the advantage of good safety profile and multi-target mechanisms, and are worthy for further investigation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bioorg.2024.107628 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!