Syntheses and Structure-Activity Relationships in Growth Inhibition Activity against Human Cancer Cell Lines of 12 Substituted Berberine Derivatives

In this study, quaternary berberine chloride is used as a lead compound to design and synthesize a series of berberine-12-amine derivatives to evaluate the growth inhibition activity against human cancer cell lines. Forty-two compounds of several series were obtained. The quaternary berberine-12- -di- -alkylamine chlorides showed the targeted activities with the IC values of most active compounds being dozens of times those of the positive control. A significant structure-activity relationship (SAR) was observed. The activities of quaternary berberine-12- -di- -alkylamine chlorides are significantly stronger than those of the reduced counterparts. In the range of about 6-8 carbon atoms, the activities increase with the elongation of -alkyl carbon chain of 12- -di- -alkylamino, and when the carbon atom numbers are more than 6-8, the activities decrease with the elongation of -alkyl carbon chain. The activities of the tertiary amine structure are significantly higher than that of the secondary amine structure.