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 (Kis 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

Synthesis, characterization, biological evaluation, and in silico studies of novel 1,3‐diaryltriazene‐substituted sulfathiazole derivatives

“…[75] The boxes enclosing the centroid of cocrystallized ligands (CJK, 53X, AA7, and N0J, respectively) were set as the grid by Receptor Grid Generation [76] in Maestro. Ligands were docked with the extra precision mode (XP) [77] of Glide, and the poses showing the highest docking score values and suitable binding interactions were subjected to an MM-GBSA (molecular mechanics/generalized Born surface area)-based refinement [78] in the Prime module.…”

New Isoindole‐1,3‐dione Substituted Sulfonamides as Potent Inhibitors of Carbonic Anhydrase and Acetylcholinesterase: Design, Synthesis, and Biological Evaluation

“…The molecular docking analyses were performed to affirm the binding characteristics of isoindole‐1,3‐dione substituted sulfonamides ( 3, 4 a – k ) on hCA isoforms I, II and AChE receptors. Firstly, docking parameters and prepared grids were validated by re‐docking the native ligands 2,3,5,6‐tetrafluoro‐4‐(propylsulfanyl)benzenesulfonamide (C 9 H 9 F 4 NO 2 S 2; 3TV), 4‐[(4,6‐dimethylpyrimidin‐2‐yl)thio]‐2,3,5,6‐tetrafluorobenzenesulfonamide (C 12 H 9 F 4 N 3 O 2 S 2 ; V50), and 1‐benzyl‐4‐[(5,6‐dimethoxy‐1‐indanon‐2‐yl)methyl]piperidine (C 24 H 29 NO 3 ; E20) into respective grids of hCA I, II, and AChE, respectively.…”

“…The molecular docking analyses [46][47][48][49][50][51] were performed to affirm the binding characteristics of isoindole-1,3-dione substituted sulfonamides (3, 4 a-k) on hCA isoforms I, II and AChE receptors. Firstly, docking parameters and prepared grids were validated by re-docking the native ligands 2,3,5,6-tetrafluoro-4-(propylsulfanyl)benzenesulfonamide (C 9 H 9 F 4 NO 2 S 2; 3TV), [52] 4- Table 5.…”

Sulfonamides incorporating ketene N,S‐acetal bioisosteres as potent carbonic anhydrase and acetylcholinesterase inhibitors

“…[ 82 ] Three‐dimensional ligand structures were prepared by the LigPrep tool [ 83 ] and implemented for their minimization states at neutral pH (7.0 ± 0.5) with Epik. [ 84 ] Extra precision Glide protocol [ 85 ] in Schrödinger Suite [ 86 ] was performed and bioactive compound structures were treated as flexible to obtain five poses for each ligand. The Prime MM–GBSA module [ 87 ] (Schrödinger Release 2019‐3) using the VSGB solvent model [ 88 ] and OPLS3e force field [ 89 ] was applied to calculate the binding free energy (ΔG Bind) of the synthesized derivatives ( 7a – o ) toward the receptors (5E2M, 6H29, and 4M0E).…”