Design, Synthesis, and Biological Activity of Chalcone Analogs Containing 4-Phenylquinolin and Benzohydrazide

A series of chalcone derivatives (3a-3m) containing 4-phenylquinoline and benzohydrazide were designed and synthesized, and their anti-inflammatory, analgesic, and antidepressant activities were evaluated. Using the classic antidepressant model, except for compounds 3a and 3d, 11 compounds all showed certain antidepressant activity at a dose of 100 mg/kg, among which compounds 3f, 3h, and 3m showed good antidepressant activity (inhibition rate, respectively 63.0 %, 73.2 %, and 76.4 %), which was equivalent to the positive control fluoxetine (inhibition rate of 70.0 %). Secondly, the inhibitory activity of these compounds on mouse MAO(A) was evaluated. At 10 mM, compounds 3f and 3j showed a certain selective inhibitory effect on mouse MAO(A), while compounds 3b, 3d, 3g, 3i, and 3m had a good inhibitory effect on mouse MAO(A) (inhibition rate is 42.3-71.4 %). The mouse ear edema model was used to evaluate the anti-inflammatory activity of compounds 3a-3m. At 30 mg/kg, compounds 3b, 3c, 3e, 3f, 3g, and 3m showed certain anti-inflammatory effects (inhibition rate of 51.5-99.9 %), which was equivalent to the positive control indomethacin (inhibition rate of 69.7 %). Results of the acetic acid-induced abdominal writhing test showed that, at 30 mg/kg, excepted for compounds 3a, 3b and 3d, all the other 10 compounds can show certain analgesic activity (inhibition rate 67-99.9 %). The use of Auto dock Vina (simina) to simulate molecular target docking shows that the development of quinoline and benzohydrazide groups is of great significance to MAO(A) inhibitors.

Automated summary

A series of chalcone derivatives containing 4-phenylquinoline and benzohydrazide were designed and synthesized. These compounds showed significant anti-inflammatory, analgesic, and antidepressant activities. The development of quinoline and benzohydrazide groups was found to be crucial for the inhibition of MAO(A).