Synthesis, Antibacterial and Pharmacokinetic Evaluation of Novel Derivatives of Harmine N 9 -Cinnamic Acid

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-08, Vol.26 (16)
• Main Authors: Liang, Yan, He, Dian, Zhou, Deshun, Li, Junshuai, Tang, Lei, Wang, Zhen
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacokinetics; Cell Death - drug effects; Cell Line, Tumor; Cinnamates - administration & dosage; Cinnamates - chemical synthesis; Cinnamates - chemistry; Cinnamates - pharmacokinetics; Female; Humans; Injections, Intravenous; Male; Microbial Sensitivity Tests; Molecular Conformation; Rats; Rats, Sprague-Dawley; Time Factors
• ISSN: 1420-3049
• DOI: 10.3390/molecules26164842

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%.