A novel templates of piperazinyl-1,2-dihydroquinoline-3-carboxylates: Synthesis, anti-microbial evaluation and molecular docking studies

作者：Banu Saleha; Bollu Rajitha; Naseema Mohammad; Gomedhika P Mary; Nagarapu Lingaiah^*; Sirisha K; Kumar C Ganesh; Gundasw Shravan Kumar

来源：Bioorganic & Medicinal Chemistry Letters, 2018, 28(7): 1166-1170.

DOI：10.1016/j.bmcl.2018.03.007

• 1, 2-Dihydroquinoline
• Piperazines
• Antimicrobial activity
• Molecular docking
• Dehydrosqualene synthase

A series of piperazinyl-1,2-dihydroquinoline carboxylates were synthesized by the reaction of ethyl 4-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylates with various piperazines and their structures were confirmed by H-1 NMR, C-13 NMR, IR and mass spectral analysis. All the synthesized compounds were screened for their in vitro antimicrobial activities. Further, the in silico molecular docking studies of the active compounds was performed to explore the binding interactions between piperazinyl-1,2-dihydroquinoline carboxylate derivatives and the active site of the Staphylococcus aureus (CrtM) dehydrosqualene synthase (PDB ID: 2ZCQ). The docking studies revealed that the synthesized derivatives showed high binding energies and strong H-bond interactions with the dehydrosqualene synthase validating the observed antimicrobial activity data. Based on antimicrobial activity and docking studies, the compounds 9b and 10c were identified as promising antimicrobial lead molecules. This study might provide insights to identify new drug candidates that target the S. aureus virulence factor, dehydrosqualene synthase.

• 出版日期2018-4-15