title: Bacterial Peptide Deformylase Inhibition of Tetrazole-Substituted Biaryl Acid Analogs: Synthesis, Biological Evaluations, and Molecular Docking Study.
abstract: The synthesis and screening of tetrazole-substituted biaryl acid analogs 7a-l as bacterial peptide deformylase (PDF) enzyme inhibitors is reported. The compounds 7e (IC50value = 5.50 μM) and 7g (IC50value = 7.25 μM) showed good PDF inhibition activity. The compounds 7e (MIC range = 10.75-11.66 μg/mL) and 7g (MIC range = 8.91-12.83 μg/mL) also showed potent antibacterial activity when compared with the standard ciprofloxacin (MIC range = 25-50 μg/mL). Thus, the active derivatives were not only potent PDF enzyme inhibitors but also efficient antibacterial agents. In order to gain more insight into the binding mode of the compounds with the PDF enzyme, the most active compounds 7e and 7g, the moderately active compound 7k, and the least active compound 7h were docked against the PDF enzyme of Escherichia coli. The docking study of the most active compounds 7e and 7g against the PDF enzyme exhibited good binding properties. Hence, we believe our synthesized compounds 7a-l could serve as reservoir for bacterial PDF inhibitor development.
authors.affiliation: Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad, India.
authors.forename: Firoz A Kalam
authors.initials: FA
authors.lastname: Khan
authors.affiliation: Department of Biotechnology, Savitribai Phule Pune University, Pune, India.
authors.forename: Rajendra H
authors.initials: RH
authors.lastname: Patil
authors.affiliation: Department of Biotechnology, Savitribai Phule Pune University, Pune, India.
authors.forename: Manjiri
authors.initials: M
authors.lastname: Patil
authors.affiliation: Department of Molecular Genetics and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Rohidas
authors.initials: R
authors.lastname: Arote
authors.affiliation: Shivaji University, Vidyanagar, Kolhapur, India.
authors.forename: Devanand B
authors.initials: DB
authors.lastname: Shinde
authors.affiliation: Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad, India.
authors.forename: Jaiprakash N
authors.initials: JN
authors.lastname: Sangshetti
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D013777:Tetrazoles; D002939:Ciprofloxacin; D000581:Amidohydrolases; C084507:peptide deformylase
keywords: Antibacterial activity; Molecular docking study; Peptide deformylase enzyme inhibitors; Tetrazole-substituted biaryl acid analogs