DefinePK

Abstract

Background: Antibiotic resistance is a major global threat to the efficacy of bacterial infection treatment. Resistance to beta-lactam antibiotics in bacteria is primarily caused by the production of extended-spectrum-lactamases, with the CTX-M variant, particularly CTX-M-15, being the most common. The need for an effective CTX-M-15 inhibitor is currently pressing. Methods: This study screened a library of natural compounds from the ZINC database against the CTX-M-15 protein using the PyRx 0.8 tool. The SwissADME web platform was used to predict the ADMET properties of the five most promising compounds. Result: The identified hits compounds, ZINC1857626342, ZINC403692, ZINC408773, ZINC57926, and ZINC790938591 exhibited strong binding with CTX-M-15. These compounds interacted with crucial catalytic site residues in the CTX-M-15 protein, particularly Ser70 and Ser130. Notably, the binding energies of these compounds were higher than those of the reference compound avibactam. Furthermore, they exhibited pharmacologically favorable characteristics. Conclusion: These compounds show promise as potential CTX-M-15 inhibitors to combat bacterial resistance. However, more experimental research is needed to optimize these compounds for their role as CTX-M-15 inhibitors.