TY - JOUR
T1 - Antibacterial activity and mechanism of action of the benzazole acrylonitrile-based compounds
T2 - In vitro, spectroscopic, and docking studies
AU - AlNeyadi, Shaikha S.
AU - Salem, Alaa A.
AU - Ghattas, Mohammad A.
AU - Atatreh, Noor
AU - Abdou, Ibrahim
N1 - Publisher Copyright:
© 2017 Elsevier Masson SAS
PY - 2017
Y1 - 2017
N2 - A new series of pyrimidine derivatives 5, 9a-d and 12a-d was synthesized by an efficient procedure. The antibacterial activity of the new compounds was studied against four bacterial strains. Compound 5 was found to exhibit the highest potency, with = 1.0 μg/ml, against both Escherichia coli and Pseudomonas aeruginosa when compared with amoxicillin (MIC = 1.0–1.5 μg/mL). Transmission electron microscope results confirmed that activities against bacteria occurred via rupturing of the cell wall. Molecular modeling results suggested that compounds 5, 9a-d and 12a-d have the potential to irreversibly bind to the penicillin-binding protein (PBP) Ser62 residue in the active site and were able to overcome amoxicillin resistance in bacteria by inhibiting the β-lactamase enzyme. Docking studies showed that compounds 5, 9a-d and 12a-d inhibit the β-lactamase enzyme through covalent bonding with Ser70. The synergistic effect with amoxicillin was studied. The newly synthesized compounds reported in this study warrant further consideration as prospective antimicrobial agents.
AB - A new series of pyrimidine derivatives 5, 9a-d and 12a-d was synthesized by an efficient procedure. The antibacterial activity of the new compounds was studied against four bacterial strains. Compound 5 was found to exhibit the highest potency, with = 1.0 μg/ml, against both Escherichia coli and Pseudomonas aeruginosa when compared with amoxicillin (MIC = 1.0–1.5 μg/mL). Transmission electron microscope results confirmed that activities against bacteria occurred via rupturing of the cell wall. Molecular modeling results suggested that compounds 5, 9a-d and 12a-d have the potential to irreversibly bind to the penicillin-binding protein (PBP) Ser62 residue in the active site and were able to overcome amoxicillin resistance in bacteria by inhibiting the β-lactamase enzyme. Docking studies showed that compounds 5, 9a-d and 12a-d inhibit the β-lactamase enzyme through covalent bonding with Ser70. The synergistic effect with amoxicillin was studied. The newly synthesized compounds reported in this study warrant further consideration as prospective antimicrobial agents.
KW - Antibacterial
KW - Docking
KW - PBP
KW - Pyrimidine
KW - Synthesis
KW - β-lactamase
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U2 - 10.1016/j.ejmech.2017.05.010
DO - 10.1016/j.ejmech.2017.05.010
M3 - Article
C2 - 28500995
AN - SCOPUS:85019082625
SN - 0223-5234
VL - 136
SP - 270
EP - 282
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -