Anticancer, Anti‐Inflammatory, and Acute Toxicological Evaluation of the Novel Berberine Derivative BN‐7

Berberine (BBR) is a traditional Chinese medicine which has been extensively utilized in treating various diseases. By cyclizing the 8- and 9-positions of berberine, a novel derivative, 2,3-dimethyldioxy-9-methyl-11-methoxy-8,10-cycloberberine chloride (BN-7), was synthesized for the first time. Its anticancer and anti-inflammatory activities, as well as acute toxicity profile, were also evaluated. BN-7 demonstrated potent antiproliferative activity, effectively suppressing the growth of two non-small cell lung cancer (NSCLC) cell lines through paraptosis. It also significantly inhibited the production of proinflammatory cytokines in LPS-stimulated RAW264.7 and THP-1 cells. Furthermore, acute toxicity studies following intravenous administration revealed that the median lethal dose (LD₅₀) of BN-7 was 7.42 mg/kg (95% CI: 6.09-9.15) in Institute of Cancer Research (ICR) mice; and 11.82 mg/kg (95% CI: 9.80-14.43) in Sprague Dawley (SD) rats. No significant changes were found in mortality, behavior, body weight, organ coefficients, or pathological observation at the dose of 5.25 mg/kg. Therefore, our findings provide novel insights into BN-7, indicating its potential as an anticancer and anti-inflammatory agent.