Identification of novel pyrazole and benzimidazole based derivatives as PBP2a inhibitors: Design, synthesis, and biological evaluation | ||||
Archives of Pharmaceutical Sciences Ain Shams University | ||||
Article 7, Volume 3, Issue 2 - Serial Number 6, June 2019, Page 228-245 PDF (1.56 MB) | ||||
Document Type: Original Article | ||||
DOI: 10.21608/aps.2019.16625.1010 | ||||
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Authors | ||||
Menna-Allah W. Shalaby ![]() | ||||
1Pharmaceutical Chemistry Department Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt. | ||||
2Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt | ||||
3Dean Faculty of Pharmacy, Sadat University in Egypt, Professor of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt | ||||
Abstract | ||||
The antibiotic resistance of methicillin-resistant Staphylococcus aureus (MRSA) is attributable to the expression of the high molecular mass transpeptidase enzyme, penicillin-binding protein 2a (PBP2a), an enzyme that catalyzes the cross-linking reaction step in the cell wall biosynthesis in the face of the challenge by β-lactam antibiotics. In the current study, ten pyrazole and benzimidazole based-compounds were designed, synthesized, and evaluated as anti-MRSA agents. These derivatives were screened for their antibacterial activity against two Staphylococcus (S.) aureus strains; methicillin-sensitive Staphylococcus aureus (MSSA) ATTC6538 and MRSA USA300 strains. Three of the tested compounds (XII, XIII, and XIV) exhibited moderate bactericidal activity against MSSA, MRSA, and vancomycin-resistant Staphylococcus aureus (VRSA) strains. Docking of these compounds into the allosteric site of PBP2a showed comparable binding modes to that of the lead quinazolinone PBP2a inhibitors suggesting a similar mode of action. The present study presents a promising candidate for further optimization as a potential PBP2a inhibitor targeting MRSA infection. | ||||
Keywords | ||||
Pyrazoles; benzimidazoles; resistance; penicillin-binding protein 2a inhibitors; anti-MRSA agents | ||||
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