RAPID COMMUNICATIONS IN MASS SPECTROMETRY
·
2025
·Vol. 39
·期 9
·e9995
·
IF 1.7
Guixiang Yang,Yalan Cui,Xingxing Zong,Qian Jin,Yi Zhang,Liqin Li,Dongxin Liu,Xuejun Chen,Chen Wang,Jingchen Wei
Rationale N -[2-Hydroxy-3,5-dimethylbenzilidene]-Hup A (H14) is a derivative of huperzine A (Hup A) that demonstrates superior protective effects against soman (GD) compared to Hup A. This study aims to evaluate the protective efficacy of H14 pretreatment against GD in rats and to provide an analytical framework for the pharmacokinetic evaluation of H14 in experimental animals. Methods The study employed protective ratios (PR) as an evaluation criterion to assess the efficacy of H14 and Hup A in preventing GD in vivo. Liquid–liquid extraction techniques were utilized to extract H14 and its metabolite, Hup A, from plasma. The extracted plasma samples were then analyzed using an ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method for the simultaneous quantification of H14 and Hup A. Results The PR values for the 6- and 12-h Hup A groups were 1.26 and 1.08, respectively. In contrast, the 6, 12, and 24-h H14 groups demonstrated PR values of 2.81, 1.98, and 1.18, respectively, indicating extended protective capabilities compared to Hup A. All validation parameters for the UHPLC–MS/MS method, including linearity, specificity, precision, accuracy, matrix effect, and stability, met the acceptance criteria established by FDA guidelines. The pharmacokinetic analysis indicates that H14, after conversion to Hup A in vivo, significantly extends the duration of Hup A concentrations in the body, leading to more effective prevention of GD poisoning compared to Hup A alone. Conclusions H14 demonstrates superior efficacy in preventing GD poisoning compared to Hup A. Furthermore, this analytical approach offers a reliable and efficient method for the pharmacokinetic evaluation of H14 in experimental animals.
研究领域:
药理学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 5
·827
·
IF 3.06
Shengsong Li,Yongchao Zheng,Weiqiang Chen,Meiling Zheng,He Zheng,Zhe Zhang,Yan Cui,Jinyi Zhong,Chonglin Zhao
Here, we introduced a novel thiourea-based rhodamine compound as a chromo-fluorogenic indicator of nerve agent Soman and its simulant diethyl chlorophosphate (DCP). The synthesized probe N-(rhodamine B)-lactam-2-(4-cyanophenyl) thiourea (RB-CT), which has a rhodamine core linked by a cyanophenyl thiosemicarbazide group, enabled a rapidly and highly sensitive response to DCP with clear fluorescence and color changes. The detection limit was as low as 2 × 10−6M. The sensing mechanism showed that opening of the spirolactam ring following the phosphorylation of thiosemicarbazides group formed a seven-membered heterocycle adduct, according to MS analysis and TD-DFT calculations. RB-CT exhibited high detecting selectivity for DCP, among other organophosphorus compounds. Moreover, two test kits were employed and successfully used to detect real nerve agent Soman in liquid and gas phase.Keywords:Nerve agents;Soman;Rhodamine B;Thiosemicarbazide;Chromo-fluorogenic probe;Detection
研究领域:
化学
·
环境科学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2023
·
IF 3.8
Yalan Cui,Xuejun Chen,Jingjing Shi,Qian Jin,Ruihua Zhang,Tong Shi,Chen Wang,Liqin Li
Pre-administration of huperzine A (Hup A) was validated to prevent poisoning from exposure to nerve agents (NAs) by reversibly inhibiting acetylcholinesterase (AChE). However, like the currently commonly used reversible inhibitors, Hup A has a short half-life and is unable to produce a long-term preventative effect. To extend the protective time of Hup A against NAs, 42 derivatives with a C N bond were designed based on the structure of Hup A in this study. All designed derivatives showed good binding capability with AChE via molecular docking. Six compounds (H3, H4, H11, H14, H16, and H25) with representative structures were selected for synthesis by Schiff base reaction, and their structures were stable. The modified Ellman's method showed the six compounds concentration-dependently inhibited AChE, and the half maximal inhibitory concentration (IC 50 ) were higher than that of Hup A. Pretreatment of AChE with the derivatives significantly increased the IC 50 of soman . In vivo experiments demonstrated H3, H4, H14, H16, and H25 had longer protective capacities against 1 × LD 95 soman-induced death in mice than Hup A. The 12 h protective index showed that the protective ratios of H3, H4, H14 and H16 were 2.31, 1.85, 2.23 and 1.99 respectively, better than that of Hup A. The extended protection of the derivatives against soman may be explained by their transformation to Hup A in vivo. Furthermore, all six compounds showed lower acute oral toxicity than Hup A. Overall, our study provided an optional strategy to acquire pretreatment agents for NAs with extended action and low toxicity.
研究领域:
药理学
·
毒理学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2020
·Vol. 49
·期 24
·8122-8135
·
IF 4.174
Jialin Yu,Qi Gao,Lijuan Zhang,Yunshan Zhou,Yuxu Zhong,Jianbo Yin,Yuanyuan Zhou,Fangsheng Tao,Yong'an Wang
ε-[Al13O4(OH)24(H2O)12]7+, which shares similarity with the phosphotriesterase active site ZnII–OH–ZnII, was specially chosen to interact with the cluster α-PMo10V2O405− to form a new three-dimensional intercluster, which crystallized in the monoclinic space group P21/m with Z = 2, for the decontamination of chemical warfare agents. The experimental results showed that 50 mg of the compound decontaminated 96.4% (within 120 min) and 99.5% (within 40 min) of sulfur mustard (HD) (4 μL) and soman (GD) (4 μL), respectively, in ambient conditions. The decontamination processes followed first-order reaction kinetics with a rate constant and half-life of 0.01234 min−1 and 56.15 min for HD and 0.1198 min−1 and 5.78 min for GD, respectively. It was concluded that the α-PMo10V2O405− moiety was responsible for the catalytic oxidation of HD into non-toxic sulfoxide, while the ε-[Al13O4(OH)24(H2O)12]7+ moiety was responsible for the catalytic hydrolysis of HD and GD into nontoxic hydrolysates. Besides, the compound showed notable efficacy for the decontamination of HD on guinea pig skin and of GD on Kunming mouse skin, indicating high potential for use in human skin protection and treatment.
研究领域:
化学
·
生物学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2022
·
IF 4.132
Guoqing Wu,Dongjiu Zhang,Wei Xu,Hongjun Zhang,Likun Chen,Yongchao Zheng,Yi Xin,Hong Li,Yan Cui
Chemical warfare agents (CWAs) can be absorbed in polymeric coatings through absorption and permeation, thus presenting a lethal touch and vapor hazards to people. Developing a highly impermeable polymer coating against CWAs, especially against organophosphate CWAs (OPs), is challenging and desirable. Herein, fluorinated epoxy (F-EP) and epoxy (EP) coatings with different cross-link densities were prepared to resist OPs. The effects of the polymer coating structure, including cross-link density, chemical composition and free volume, on the chemical resistance to dimethyl methylphosphonate (DMMP, Soman simulant) were investigated in detail. Meanwhile, the chemical resistance to Soman and VX was examined. The results reveal that the cross-link density is a critical factor in determining the chemical resistance of the coatings. Highly cross-linked EP and F-EP coatings with dense and solid cross-linked networks can fully bar DMMP and OPs permeation during the test time. At low or medium cross-link densities, the EP coating with a lower retention of DMMP exhibited a higher resistance than the F-EP coating due to the lower interaction with DMMP and smaller free-volume holes and lower relative fractional free volume. These results suggest that increasing the cross-link density is a reasonable approach to control the chemical resistance of polymer networks against OPs.
研究领域:
材料科学
·
高分子化学
·
化学工程
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）