Synthesis and DNA-binding affinities of protoberberine-based multivalent agents.

Three novel berberine derivatives bearing two, three, and four primary amino groups at C(9), respectively, were synthesized and characterized on the basis of ¹H- and ¹³C-NMR, MS, and HR-MS data. Their non-covalent binding with calf thymus (CT) DNA was investigated by means of spectrophotometric titration and ethidium bromide (EB) displacement experiments. The results indicated that these multivalent berberine derivatives exhibited up to 130-fold enhanced binding affinities relative to berberine, and thus, may be exploitable as potent DNA-binding agents.