Unveiling the antibacterial efficacy of thiazolo [3,2‐a] pyrimidine: Synthesis, molecular docking, and molecular dynamic simulation

Two series of C‐Mannich base derivatives were synthesized and evaluated through the reaction of formaldehyde, two thiazolo‐pyrimidine compounds, and various 2°‐amines. The chemical structures and inherent properties of the synthesized compounds were authenticated using a variety of spectroscopic tec...

Full description

Saved in:
Bibliographic Details
Published in:Journal of biochemical and molecular toxicology 2024-09, Vol.38 (9), p.n/a
Main Authors: Patel, Vishant C., Patel, Ankit J., Patel, Darshan S., Dholakia, Amit B., Ansari, Siddique Akber, Agrawal, Mohit
Format: Article
Language:English
Subjects:
Amines
Ampicillin
Antibacterial activity
Antibacterial agents
Antiinfectives and antibacterials
Bacillus megaterium
Bacillus subtilis
Bacteria
Binding
Chemical compounds
Chemical synthesis
Deoxyribonucleic acid
dihydropyrimidones
DNA
DNA biosynthesis
DNA topoisomerase
E coli
Effectiveness
Enzymes
Escherichia coli
Formaldehyde
Heterocyclic amines
Mannich base
MD simulation
Minimum inhibitory concentration
Molecular docking
Molecular dynamics
Pyrimidines
Replication
Stability
Staphylococcus aureus
thiazolo‐pyrimidine
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Two series of C‐Mannich base derivatives were synthesized and evaluated through the reaction of formaldehyde, two thiazolo‐pyrimidine compounds, and various 2°‐amines. The chemical structures and inherent properties of the synthesized compounds were authenticated using a variety of spectroscopic techniques. The aseptic bactericidal potential of the compounds was assessed alongside five common bacterial microbes, with Ampicillin employed as the reference drug. Compounds 9b and 9d demonstrated comparable antibacterial activity to ampicillin against Bacillus subtilis and Bacillus megaterium, respectively, at 100 μg/mL. Furthermore, compounds 9f and 10f exhibited noteworthy action against Staphylococcus aureus (MIC: 250 μg/mL). Compounds 10b and 10f displayed excellent efficacy versus Escherichia coli, boasting (MIC: 50 μg/mL). Molecular docking studies elucidated the necessary connections and energies of molecular entities with the E. coli DNA gyrase B enzyme, a pivotal target in bacterial DNA replication. Further thermodynamic stability of the ligand‐receptor complex of 10b and 10f were further validated though 200 ns molecular dynamics simulation. The findings highlight the potential of these synthesized derivatives as effective antibacterial agents and provide valuable insights into their mechanism of action. Two series of C‐Mannich base derivatives were synthesized by reacting formaldehyde, two thiazolo[3,2‐a] pyrimidine compounds, and seven heterocyclic amines. The antibacterial potential of the compounds was evaluated against five common bacterial pathogens, with Ampicillin as the reference drug. Compounds 9b and 9d showed comparable antibacterial activity to Ampicillin against Bacillus subtilis and Bacillus megaterium, respectively, at 100 μg/mL. Compounds 9 f and 10 f exhibited notable activity against Staphylococcus aureus, with MIC values of 250 μg/mL. Compounds 10b and 10 f displayed excellent efficacy against Escherichia coli, with MIC values of 50 μg/mL. Molecular docking studies revealed the binding interactions and energies of the compounds with the E. coli DNA gyrase B enzyme, a crucial target in bacterial DNA replication. The binding stability of the promising compounds 10b and 10f was further validated through 200 ns molecular dynamics (MD) simulations. Highlights Two series of C‐Mannich base derivatives were synthesized by reacting formaldehyde, two thiazolo[3,2‐a] pyrimidine compounds, and seven heterocyclic amines. The antibacterial poten
ISSN:1095-6670
1099-0461
DOI:10.1002/jbt.23822