Synthesis of berberine derivatives and their antiviral activity toward respiratory syncytial virus

A series of derivatives of berberine was synthesized to estimate their antiviral activity toward respiratory syncytial virus. Berberine and its hydrogenated analogs were modified at different positions with various substituents. The antiviral activity of berberine and its derivatives against respiratory syncytial virus strain A2 was studied in vitro. Berberine itself and its 12-nitro and 9-O derivatives having heterocyclic motifs in the substituent were shown to have the highest antiviral activity, with half-maximal inhibitory concentration in the lower range (<10 mu M). It was found that half-maximal cytotoxic concentration of the compounds varies widely, from 9 to >2000 mu M. The selectivity of most compounds under study was below a desired threshold; only berberine, 12-nitroberberine, and tetrahydroberberine can be considered promising for the development of drugs for respiratory syncytial infection. [Graphics] .