Design, synthesis, molecular docking, density functional theory and antimicrobial studies of some novel benzoxazole derivatives as structural bioisosteres of nucleotides

J Biomol Struct Dyn. 2021 Jun;39(9):3080-3091. doi: 10.1080/07391102.2020.1760134. Epub 2020 May 13.

Abstract

A series of some novel 2-(p-tert-butylphenyl)-5-(3-substituted-propionamido)benzoxazole derivatives have been designed, synthesized, evaluated for antimicrobial activity and have performed molecular docking studies against penicillin-binding protein 4 (PBP4) and active and allosteric site of PBP2a; were calculated some theoretical quantum parameters and absorption, distribution, metabolism and excretion (ADME) descriptors. B9 acted at minimum inhibitory concentration (MIC) = 8 µg/mL against S. aureus, E. faecalis and their drug-resistant isolates and also formed with GLU145 (1.74 Å) and ILE144 (1.89 Å) two hydrogen bonds at allosteric site of PBP2a with Glide emodel score: -42.168. ΔE of compound B9 had moderate value of all compounds with 0.14742.[Formula: see text]Communicated by Ramaswamy H. Sarma.

Keywords: ADME prediction; DFT; antimicrobial activity; benzoxazole; molecular docking.

MeSH terms

  • Anti-Infective Agents* / pharmacology
  • Benzoxazoles* / pharmacology
  • Density Functional Theory
  • Molecular Docking Simulation
  • Nucleotides
  • Staphylococcus aureus

Substances

  • Anti-Infective Agents
  • Benzoxazoles
  • Nucleotides