Synthesis, Antibacterial and Pharmacokinetic Evaluation of Novel Derivatives of Harmine N-Cinnamic Acid.

A series of 16 new derivatives of harmine N-Cinnamic acid were synthesized and fully characterized using NMR and MS. The in vitro antibacterial evaluation revealed that most of the synthesized harmine derivatives displayed better antibacterial activities against Gram-positive strains (, and MRSA) than Gram-negative strains ( and PA). In particular, compound showed the strongest bactericidal activity with a minimum inhibitory concentration of 13.67 μg/mL. MTT assay showed that compound displayed weaker cytotoxicity than harmine with IC of 340.30, 94.86 and 161.67 μmol/L against WI-38, MCF-7 and HepG2 cell lines, respectively. The pharmacokinetic study revealed that the distribution and elimination of in vivo were rapid in rats with an oral bioavailability of 6.9%.