Identification of novel pyrazole and benzimidazole based derivatives as PBP2a inhibitors: Design, synthesis, and biological evaluation
Shalaby, M., Dokla, E., Serya, R., Abouzid, K. (2019). Identification of novel pyrazole and benzimidazole based derivatives as PBP2a inhibitors: Design, synthesis, and biological evaluation. EKB Journal Management System, 3(2), 228-245. doi: 10.21608/aps.2019.16625.1010
Menna-Allah W. Shalaby; Eman M.E. Dokla; Rabah A. T. Serya; Khaled A. M. Abouzid. "Identification of novel pyrazole and benzimidazole based derivatives as PBP2a inhibitors: Design, synthesis, and biological evaluation". EKB Journal Management System, 3, 2, 2019, 228-245. doi: 10.21608/aps.2019.16625.1010
Shalaby, M., Dokla, E., Serya, R., Abouzid, K. (2019). 'Identification of novel pyrazole and benzimidazole based derivatives as PBP2a inhibitors: Design, synthesis, and biological evaluation', EKB Journal Management System, 3(2), pp. 228-245. doi: 10.21608/aps.2019.16625.1010
Shalaby, M., Dokla, E., Serya, R., Abouzid, K. Identification of novel pyrazole and benzimidazole based derivatives as PBP2a inhibitors: Design, synthesis, and biological evaluation. EKB Journal Management System, 2019; 3(2): 228-245. doi: 10.21608/aps.2019.16625.1010

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, Pages 228-245    PDF (1.56 M)
Document Type: Original Article
DOI: 10.21608/aps.2019.16625.1010
Authors
Menna-Allah W. Shalaby* 1; Eman M.E. Dokla1; Rabah A. T. Serya2; Khaled A. M. Abouzid3
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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