Synthesis, Antibacterial and Pharmacokinetic Evaluation of Novel Derivatives of Harmine N<sup>9</sup>-Cinnamic Acid
Yan Liang,
Dian He,
Deshun Zhou,
Junshuai Li,
Lei Tang,
Zhen Wang
Affiliations
Yan Liang
School of Pharmacy, Lanzhou University, West Donggang Road No. 199, Lanzhou 730000, China
Dian He
School of Pharmacy, Lanzhou University, West Donggang Road No. 199, Lanzhou 730000, China
Deshun Zhou
Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agriculture Sciences, No. 335, Qilihe District, Lanzhou 730050, China
Junshuai Li
Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agriculture Sciences, No. 335, Qilihe District, Lanzhou 730050, China
Lei Tang
Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agriculture Sciences, No. 335, Qilihe District, Lanzhou 730050, China
Zhen Wang
School of Pharmacy, Lanzhou University, West Donggang Road No. 199, Lanzhou 730000, China
A series of 16 new derivatives of harmine N9-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 (S. aureus, S. albus and MRSA) than Gram-negative strains (E. coli and PA). In particular, compound 3c showed the strongest bactericidal activity with a minimum inhibitory concentration of 13.67 μg/mL. MTT assay showed that compound 3c displayed weaker cytotoxicity than harmine with IC50 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 3c in vivo were rapid in rats with an oral bioavailability of 6.9%.
