Identification of novel pyrazole and benzimidazole based derivatives as PBP2a inhibitors: Design, synthesis, and biological evaluation
Shalaby, Menna-Allah; Dokla, Eman; Serya, Rabah; Abouzid, Khaled;
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.
Other data
Title | Identification of novel pyrazole and benzimidazole based derivatives as PBP2a inhibitors: Design, synthesis, and biological evaluation | Authors | Shalaby, Menna-Allah; Dokla, Eman ; Serya, Rabah ; Abouzid, Khaled | Keywords | Pyrazoles;MRSA agents;penicillin-binding protein 2a inhibitors;benzimidazoles;resistance | Issue Date | 2019 | Publisher | Egyptian knowledge bank | Journal | Archives of Pharmaceutical Sciences Ain Shams University | Volume | 3 | Issue | 2 | Start page | 228 | End page | 245 | ISSN | 2356-8399 | DOI | 10.21608/aps.2019.16625.1010 |
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