title: Design and synthesis of 4'-((5-benzylidene-2,4-dioxothiazolidin-3-yl)methyl)biphenyl-2-carbonitrile analogs as bacterial peptide deformylase inhibitors.
abstract: Herein, we report the synthesis and screening of 4'-((5-benzylidene-2,4-dioxothiazolidin-3-yl)methyl)biphenyl-2-carbonitrile analogs 11(a-j) as bacterial peptide deformylase (PDF) enzyme inhibitors. The compounds 11b (IC50value = 139.28 μm), 11g (IC50value = 136.18 μm), and 11h (IC50value = 131.65 μm) had shown good PDF inhibition activity. The compounds 11b (MIC range = 103.36-167.26 μg/mL), 11g (MIC range = 93.75-145.67 μg/mL), and 11h (MIC range = 63.61-126.63 μg/mL) had also shown potent antibacterial activity when compared with standard ampicillin (MIC range = 100.00-250.00 μg/mL). Thus, the active derivatives were not only PDF inhibitors but also efficient antibacterial agents. To gain more insight on the binding mode of the compounds with PDF enzyme, the synthesized compounds 11(a-j) were docked against PDF enzyme of Escherichia coli and compounds exhibited good binding properties. The results suggest that this class of compounds has potential for development and use in future as antibacterial drugs.
authors.affiliation: Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad, Maharashtra, India.
authors.forename: Firoz A Kalam
authors.initials: FA
authors.lastname: Khan
authors.affiliation: Department of Biotechnology, Savitribai Phule Pune University, Pune, Maharashtra, India.
authors.forename: Rajendra H
authors.initials: RH
authors.lastname: Patil
authors.affiliation: Shivaji University, Kolhapur, Maharashtra, India.
authors.forename: Devanand B
authors.initials: DB
authors.lastname: Shinde
authors.affiliation: Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad, Maharashtra, India. jnsangshetti@rediffmail.com.
authors.forename: Jaiprakash N
authors.initials: JN
authors.lastname: Sangshetti
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D053778:Thiazolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D053778:Thiazolidines; D000581:Amidohydrolases; C084507:peptide deformylase
keywords: antibacterial activity; bacterial peptide deformylase inhibition; biphenyl; molecular docking study; thiazolidinedione