Synthesis and antifungal activity of a novel series of 13-(4-isopropylbenzyl)berberine derivatives

• Published in: Bioorganic & medicinal chemistry letters 2010-11, Vol.20 (22), p.6551-6554
• Main Authors: Park, Ki Duk, Cho, Sung Jin, Moon, Jae Sun, Kim, Sung Uk
• Format: Article
• Language: English
• Subjects: 13-(4-Isopropylbenzyl)berberine; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal activity; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Aspergillus; Aspergillus - drug effects; Berberine - chemical synthesis; Berberine - chemistry; Berberine - pharmacology; Berberine derivatives; Biological and medical sciences; Candida; Candida - drug effects; Cryptococcus neoformans; Cryptococcus neoformans - drug effects; Human pathogenic fungi; Medical sciences; Mice; Microbial Sensitivity Tests; Pharmacology. Drug treatments
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.09.045

A novel series of 9-O-substituted-13-(4-isopropylbenzyl)berberine derivatives as antifungal agents was synthesized and examined the activity. By replacing the methyl group of 13-(4-isopropylbenzyl)berberine 2 with various acyl, alkyl, and benzyl groups via the demethylated intermediate, 13-(4-isopropylbenzyl)berberrubine 4, a novel series of 9-O-alkyl-13-(4-isopropylbenzyl)berberine derivatives was synthesized and examined for antifungal activities against various human pathogenic fungi. The introduction of various alkyl groups led to enhanced antifungal activity but that of acyl groups resulted in decrease of the activity. Among them, 9-O-butyl-13-(4-isopropylbenzyl)berberine 6d exhibited the most potent antifungal activities against Cryptococcus neoformans, Candida species (MIC=0.25–1μg/ml), and Aspergillus species (MIC=2–4μg/ml). The compound was found to be relatively safe up to 900mg/kg in oral administration to mice.