title: Biphenyl tetrazole-thiazolidinediones as novel bacterial peptide deformylase inhibitors: Synthesis, biological evaluations and molecular docking study.
abstract: Herein, we report the synthesis and screening of biphenyl tetrazole-thiazolidinediones 14(a-j) as bacterial Peptide deformylase (PDF) enzyme inhibitors. The compounds 14b (IC50value=16.25μM), 14c (IC50value=18.00μM) and 14h (IC50value=17.25μM) had shown good PDF inhibition activity. The compounds 14b (MIC range=20.75-35.41μg/mL), 14c (MIC range=19.41-26.00μg/mL) and 14d (MIC range=8.41-8.58μg/mL) had also shown potent antibacterial activity when compared with standard ciprofloxacin (MIC range=25-50μg/mL). Thus, the active derivatives were not only potent PDF inhibitors but also efficient antibacterial agents. In order to gain more insight on the binding mode of the compounds with PDF enzyme, the synthesized compounds 14(a-j) were docked against PDF enzyme of E. coli and compounds exhibited good binding properties. The results suggest that this class of compounds have been potential for development and use in a future as antibacterial drugs.
authors.affiliation: Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431001, M.S., India.
authors.forename: Firoz A Kalam
authors.initials: FAK
authors.lastname: Khan
authors.affiliation: Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431001, M.S., India.
authors.forename: Kaivalya S
authors.initials: KS
authors.lastname: Jadhav
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: Shivaji University, Vidyanagar, Kolhapur 416 004, M.S., India.
authors.forename: Devanand B
authors.initials: DB
authors.lastname: Shinde
authors.affiliation: Department of Molecular Genetics & Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea. Electronic address: rohi06@snu.ac.k.
authors.forename: Rohidas B
authors.initials: RB
authors.lastname: Arote
authors.affiliation: Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431001, M.S., India. Electronic address: jnsangshetti@rediffmail.com.
authors.forename: Jaiprakash N
authors.initials: JN
authors.lastname: Sangshetti
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D045162:Thiazolidinediones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D045162:Thiazolidinediones; D000581:Amidohydrolases; C084507:peptide deformylase
keywords: Antibacterial activity; Biphenyl tetrazole-thiazolidinediones; Molecular docking study; PDF inhibition