IN SILICO STUDY OF NEW SCHIFF BASE-AND AMIDE-BORONIC ACID DERIVATIVES AS POTENTIAL INHIBITORS OF Β-LACTAMASES

Abstract

Bacteria are becoming more and more resistant to β-lactam antibiotics. One approach to lower such resistance involves combining inhibitors of β-lactamase with β-lactams antibiotics. As such, the need for innovative inhibitors of β-lactamases is urgent. therefore, the aim of this research was to design and dock two new series of amides and Schiff bases of the cyclic and noncyclic boronate derivatives into four subtypes from two different classes of the β-lactamase enzymes. In silico prediction of the pharmacokinetic profile of the designed compounds was also performed. the results revealed possible enhanced activity of 15 out of the 82 compounds, when matched with 4 existing β-lactamase inhibitors (clavulanic acid, sulbactam, tazobactam and vaborbactam). the 15 compounds showed favorable docking interactions with the residues in the active site of all enzymes. the predicted pharmacokinetic characteristics also showed that the 15 compounds are promising as oral agents. the designed compounds have the potential to act as inhibitors of β-lactamase as shown by their docking results on 4 β-lactamase crystal structures. the pharmacokinetic profile of 15 compounds is also promising, making them suitable candidates for synthesis and in vitro testing.