In Vitro and in Silico Studies on the Toxic Effects of Antibacterial Drugs as Human Serum Paraoxonase 1 Inhibitor

Abstract

The core purpose of the current study was to investigate the interactions of widely used broad-spectrum antibacterial drugs developed in response to the increasing rate of antibiotic-resistant various bacteria and to contribute to the field of drug design. Also, it is to broaden the current knowledge of paraoxonase 1 enzyme (EC: 3.1.8.1; PON1) which is a crucial drug-target enzyme. For this aim, first, we purified PON1 from human serum using rapid chromatographic techniques including, enzyme precipitation, IEX (ion-exchange) chromatography, and SEC (size exclusion chromatography), quickly. Following this, we researched the inhibitory effects of some antibacterial drugs. Finally, molecular docking tests were performed and analyzed in silico data. PON1 was found to be effectively inhibited by tigecycline, linezolid, ciprofloxacin lactate, and ertapenem sodium (K(i)s in the ranging from 0.018 to 125.540 mM). Drugs showed two different inhibition mechanisms: Linezolid was competitive; others were non-competitive. While Glide GScore of the linezolid for 1 V04 and 3SRE receptors were detected to be -4.442 and -4.915 kcal/mol in the SP mode, monitored as -3.548 and -3.791 kcal/mol in the XP mode, respectively