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

• Published in: Bioorganic & medicinal chemistry letters Vol. 28; no. 7; pp. 1166 - 1170
• Main Authors: Banu, Saleha, Bollu, Rajitha, Naseema, Mohammad, Gomedhika, P. Mary, Nagarapu, Lingaiah, Sirisha, K., Kumar, C. Ganesh, Gundasw, Shravan Kumar
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.04.2018; Elsevier
• Subjects: 1, 2-Dihydroquinoline; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimicrobial activity; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Dehydrosqualene synthase; Dose-Response Relationship, Drug; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Life Sciences & Biomedicine; Microbial Sensitivity Tests; Molecular docking; Molecular Docking Simulation; Molecular Structure; Pharmacology & Pharmacy; Physical Sciences; Piperazines; Piperazines - chemical synthesis; Piperazines - chemistry; Piperazines - pharmacology; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - pharmacology; Science & Technology; Structure-Activity Relationship; Antimicrobial activity; Piperazines; Molecular docking; 1, 2-Dihydroquinoline; Dehydrosqualene synthase; DESIGN; MOIETY; ANTIPROLIFERATIVE AGENTS; QUINOLONES; QUINOLINE; STAPHYLOCOCCUS-AUREUS; INHIBITORS; DERIVATIVES; HYBRIDS
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2018.03.007

A series of piperazinyl-1,2-dihydroquinoline carboxylates have been synthesized in good to excellent yields and screened for their in vitro antimicrobial activities. Compounds 9b and 10c were identified as promising leads showing good antimicrobial profile. [Display omitted] •A series of piperazinyl-1,2-dihydroquinoline-3-carboxylates were synthesized.•Screened for their in vitro antimicrobial activities.•9b and 10c were shown significant.•In silico study active with Staphylococcus aureus 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 1H NMR, 13C 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.