Synthesis, in vitro evaluation and molecular docking of new pyrazole derivatives bearing 1,5,10,10a-tetrahydrobenzo[g]quinoline-3-carbonitrile moiety as potent antibacterial agents

Abstract

In the current study, a new series of pyrazole derivatives 4a–d, 5a–d and 6a–d possessing 1,5,10,10a-tetrahydrobenzo[g]quinoline-3-carbonitrile moiety were synthesized by treating chalcones (3a–d) with hydrazine monohydrate/acetic anhydride, hydrazine monohydrate/formic acid and 4-chlorophenylhydrazine in ethanol, respectively. These reactions proceeded smoothly with satisfactory yields, and the obtained compounds were characterized using FTIR, 1H-NMR, 13C-NMR and elemental analyses. All the synthesized compounds were subjected to antibacterial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa bacteria and molecular docking studies. The antibacterial studies showed that all compounds exhibited good to excellent antibacterial activity against the tested bacterial strains. The structure–activity relationship studies revealed that the compounds 3b, 4b, 5b and 6b bearing a chlorine atom at the para position of the phenyl group attached to pyrazole moiety in displayed the highest antibacterial activity against all the tested bacteria exceeding the standard drug ampicillin. Moreover, the molecular docking results showed that the highest scores docking have been obtained from the most active antibacterial compounds 3b, 3d, 4b, 4d, 4c, 5b and 6b with good energy binding score within the active site of topoisomerase II DNA gyrase enzymes (PDB ID: 2XCS), suggesting that they can act by the inhibition of DNA replication. These compounds are auspicious candidates as antibacterial agents that would deserve further investigations.