title: Biofilm inhibition of linezolid-like Schiff bases: synthesis, biological activity, molecular docking and in silico ADME prediction.
abstract: Herein, we report the synthesis and screening of linezolid-like Schiff bases as inhibitors of biofilm formation. The result of biofilm inhibition of Pseudomonas aeruginosa suggested that compounds 5h (IC50 value=12.97±0.33μM) and 5i (IC50 value=15.63±0.20μM) had more inhibitory activity when compared with standard linezolid (IC50=15.93±0.18μM) without affecting the growth of cells (and thus behave as anti-quorum sensing agents). The compounds 5h (MIC range=2.5-10μg/mL) and 5i (MIC range=3.5-10μg/mL) with 2-chloroquinolinyl and 2-chloro-8-methylquinolinyl motif, respectively, showed antibacterial activity in comparable range of linezolid (MIC range=2-3μg/mL) and were more potent when compared with ciprofloxacin (MIC range=25-50μg/mL). Thus, the active derivatives were not only potent inhibitors of P. aeruginosa biofilm growth but also efficient antibacterial agents. The docking study of most active compounds 5h and 5i against PqsD enzyme of P. aeruginosa exhibited good binding properties. In silico ADME properties of synthesized compounds were also analyzed and showed potential to develop as good oral drug candidates.
authors.affiliation: Dr. Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad 431001, (M.S.), India. Electronic address: jnsangshetti@rediffmail.com.
authors.forename: Jaiprakash N
authors.initials: JN
authors.lastname: Sangshetti
authors.affiliation: Dr. Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad 431001, (M.S.), India.
authors.forename: Firoz A Kalam
authors.initials: FA
authors.lastname: Khan
authors.affiliation: Department of Biotechnology, Savitribai Phule Pune University, Pune 411007, (M.S.), India.
authors.forename: Rajendra H
authors.initials: RH
authors.lastname: Patil
authors.affiliation: Department of Biotechnology, Savitribai Phule Pune University, Pune 411007, (M.S.), India.
authors.forename: Sayali D
authors.initials: SD
authors.lastname: Marathe
authors.affiliation: Department of Biotechnology, Savitribai Phule Pune University, Pune 411007, (M.S.), India.
authors.forename: Wasudev N
authors.initials: WN
authors.lastname: Gade
authors.affiliation: Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004, (M.S.), India.
authors.forename: Devanand B
authors.initials: DB
authors.lastname: Shinde
mesh_terms: D000081:Acetamides / Q000737:chemistry / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms; D003198:Computer Simulation; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D062105:Molecular Docking Simulation; D023303:Oxazolidinones / Q000737:chemistry / Q000494:pharmacology*; D012545:Schiff Bases / Q000737:chemistry*
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D012545:Schiff Bases; D000069349:Linezolid
keywords: ADME properties; Antibacterial activity; Biofilm inhibition; Linezolid-like Schiff bases; Molecular docking