Effect of Fluorine Atoms and Piperazine Rings on Biotoxicity of Norfloxacin Analogues: Combined Experimental and Theoretical Study DOI Creative Commons
Chuanxi Yang, Xiaoning Wang,

Xinyan Zhao

et al.

Environment & Health, Journal Year: 2024, Volume and Issue: 2(12), P. 886 - 901

Published: Aug. 22, 2024

To clarify the effect of fluorine atom and piperazine ring on norfloxacin (NOR), NOR degradation products (NOR-DPs, P1–P8) were generated via UV combined with hydrogen peroxide (UV/H2O2) technology. did not significantly affect cytotoxicity against BV2, A549, HepG2, Vero E6 cells. Compared that NOR, mutagenicity median lethal concentration P1–P8 in fathead minnow increased, bioaccumulation factor oral dose rats decreased. Molecular docking was used to evaluate inhibitory DNA gyrase A (gyrA) NOR-DPs determine molecular-level mechanism establish structure–activity relationship. Results indicated most common amino acid residues Ile13, Ser27, Val28, Gly31, Asp36, Arg46, Arg47, Asp157, Gly340; bonds hydrophobic interactions played key roles effect. Binding area (BA) decreased from 350.80 Å2 (NOR) 346.21 (P1), absolute value binding energy (|BE|) changed 2.53 kcal/mol 2.54 indicating mainly affects BA. The clearly influenced BA |BE|. "Yang ChuanXi Rules" explain effects molecular weight (MW), BA, |BE|, sum η1 + η2 (η1: normalization η2: |BE|) predict biotoxicity based half-maximum (IC50), half-minimal (MIC50), bactericidal (MBC50) values.

Language: Английский

Ginsenoside Rg3 alleviates brain damage caused by chlorpyrifos exposure by targeting and regulating the microbial - gut - brain axis DOI
Silu Liu, Yang Yang,

Ying Zong

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: 143, P. 156838 - 156838

Published: May 10, 2025

Language: Английский

Citations

0
Potential Common Mechanisms of Cytotoxicity Induced by Organophosphorus Pesticides via NLRP3 Inflammasome Activation DOI Creative Commons
Xiao‐Ning Wang, Xin Sui, Yangyang Sun

et al.

GeoHealth, Journal Year: 2024, Volume and Issue: 8(4)

Published: April 1, 2024

Abstract The Multi‐Threat Medical Countermeasure (MTMC) technique is crucial for developing common biochemical signaling pathways, molecular mediators, and cellular processes. This study revealed that the Nod‐like receptor 3 (NLRP3) inflammasome pathway may be a significant contributor to cytotoxicity induced by various organophosphorus pesticides (OPPs). demonstrated exposure six different types of OPPs (paraoxon, dichlorvos, fenthion, dipterex, dibrom, dimethoate) led in BV2 cells, which was accompanied increased expression NLRP3 complexes (NLRP3, ASC, Caspase‐1) downstream inflammatory cytokines (IL‐1β, IL‐18), order dichlorvos > dipterex dibrom paraoxon fenthion dimethoate, based on IC 50 values 274, 410, 551, 585, 2,158, 1,527,566 μM, respectively. findings suggest targeting could potential approach broad‐spectrum antitoxic drugs combat multi‐OPPs‐induced toxicity. Moreover, inhibition efficiently protected cells against these OPPs, NLRP3, Caspase‐1, IL‐1β, IL‐18 decreased accordingly. affinity dimethoate (fenthion dipterex) K D 89.8, 325, 1,460, 2,690 Furthermore, mechanism NLRP3‐OPPs clarified presence toxicity effector groups (benzene ring, nitrogen/oxygen‐containing functional group); =O, ‐O‐, or =S (active) groups; combination residues (Gly271, Asp272). finding provided valuable insights into exploring mechanisms multiple threats effective therapeutic strategies prevent poisoning.

Language: Английский

Citations

3
Effect of Fluorine Atoms and Piperazine Rings on Biotoxicity of Norfloxacin Analogues: Combined Experimental and Theoretical Study DOI Creative Commons
Chuanxi Yang, Xiaoning Wang,

Xinyan Zhao

et al.

Environment & Health, Journal Year: 2024, Volume and Issue: 2(12), P. 886 - 901

Published: Aug. 22, 2024

To clarify the effect of fluorine atom and piperazine ring on norfloxacin (NOR), NOR degradation products (NOR-DPs, P1–P8) were generated via UV combined with hydrogen peroxide (UV/H2O2) technology. did not significantly affect cytotoxicity against BV2, A549, HepG2, Vero E6 cells. Compared that NOR, mutagenicity median lethal concentration P1–P8 in fathead minnow increased, bioaccumulation factor oral dose rats decreased. Molecular docking was used to evaluate inhibitory DNA gyrase A (gyrA) NOR-DPs determine molecular-level mechanism establish structure–activity relationship. Results indicated most common amino acid residues Ile13, Ser27, Val28, Gly31, Asp36, Arg46, Arg47, Asp157, Gly340; bonds hydrophobic interactions played key roles effect. Binding area (BA) decreased from 350.80 Å2 (NOR) 346.21 (P1), absolute value binding energy (|BE|) changed 2.53 kcal/mol 2.54 indicating mainly affects BA. The clearly influenced BA |BE|. "Yang ChuanXi Rules" explain effects molecular weight (MW), BA, |BE|, sum η1 + η2 (η1: normalization η2: |BE|) predict biotoxicity based half-maximum (IC50), half-minimal (MIC50), bactericidal (MBC50) values.

Language: Английский

Citations

0