Synthesis and biological evaluation of berberine derivatives

Berberine 1, a quaternary isoquinoline alkaloid, has a long history of use in traditional Indian and Chinese medicine. It is found in the root, rhizome and stem bark of many plant species such as Coptis japonica Makino, Berberis vulgaris L. and Hydrastis canadensis L. In various pharmacological studies, berberine has shown weak, but unspecific antibacterial, antitumoral, anti-inflammatory, antileishmanial and antiphotooxidative effects [1–5]. In this study, berberine and several natural and synthetic derivatives, both quaternary and basic, were tested for specific efficacy against bacteria and fungi, human leukemic HL-60 cells, and for inhibition of chlorophyll-sensitized photooxidation of linoleic acid. All compounds were weakly or not toxic against HL-60 cells. In the agar diffusion test, derivatives with a hydroxy group in position 9 (protoberberines of general formula, 2) were found to have the largest effect against the fungal species tested (Aspergillus niger, Hyphopichia burtonii), while berberine exhibited only marginal activity. The protoberberines perhaps inhibit 24-sterolmethyltransferase (24-SMT) [6].

Fig.1: Berberine 1 and protoberberine of general formula 2

Of all compounds, berberine showed the highest antiphotooxidative activity (61%). It was equipotent with the standard lipophilic antiphotooxidant ascorbyl palmitate, but distinguished by its water solubility. This is of interest in the conservation of food products.

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2. Kettmann, V. et al. (2004) Pharmazie 59:548–551.

3. Kuo, CL. et al. (2004) Cancer Lett. 203(2):127–137.

4. Vennerstrom, JL. et al. (1990) Antimicrob. Agents Chemother. 34:918–921.

5. Kim, JP. et al. (2000)J. Agric. Food Chem. 48:1058–1063.

6. Park, K-S. et al. (1999)J. Antimicrob. Chemother. 43:667–674.