Detection, transformation, and toxicity of indole-derivative nonsteroidal anti-inflammatory drugs during chlorine disinfection

Qiu, Jingfan; Huang, Yan; Wu, Yun; Shi, Peng; Xu, Bin; Chu, Wenhai; Pan, Yang

doi:10.1016/j.chemosphere.2020.127579

Cited by 18 publications

(8 citation statements)

References 45 publications

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“…The LC 50 value of indomethacin at 48 h on D. magna calculated in our work was 25.12 µM, a value that is close to that predicted (15.85 µM) by Qui et al [ 45 ]. Pyrroles 4a and 4d showed a lower toxicity compared with indomethacin, whereas 4b and 4c showed a significantly higher toxicity than the positive control.…”

Section: Resultssupporting

confidence: 91%

New Pyrrole Derivatives as Promising Biological Agents: Design, Synthesis, Characterization, In Silico, and Cytotoxicity Evaluation

Ivan

Bărbuceanu

Hotnog

et al. 2022

IJMS

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The current study describes the synthesis, physicochemical characterization and cytotoxicity evaluation of a new series of pyrrole derivatives in order to identify new bioactive molecules. The new pyrroles were obtained by reaction of benzimidazolium bromide derivatives with asymmetrical acetylenes in 1,2-epoxybutane under reflux through the Huisgen [3 + 2] cycloaddition of several ylide intermediates to the corresponding dipolarophiles. The intermediates salts were obtained from corresponding benzimidazole with bromoacetonitrile. The structures of the newly synthesized compounds were confirmed by elemental analysis, spectral techniques (i.e., IR, 1H-NMR and 13C-NMR) and single-crystal X-ray analysis. The cytotoxicity of the synthesized compounds was evaluated on plant cells (i.e., Triticum aestivum L.) and animal cells using aquatic crustaceans (i.e., Artemia franciscana Kellogg and Daphnia magna Straus). The potential antitumor activity of several of the pyrrole derivatives was studied by performing in vitro cytotoxicity assays on human adenocarcinoma-derived cell lines (i.e., LoVo (colon), MCF-7 (breast), and SK-OV-3 (ovary)) and normal human umbilical vein endothelial cells (HUVECs). The obtained results of the cytotoxicity assessment indicated that the tested compounds had nontoxic activity on Triticum aestivum L., while on Artemia franciscana Kellogg nauplii, only compounds 2c and 4c had moderate toxicity. On Daphnia magna, 4b and 4c showed high toxicity; 2a, 2b, and 2c moderate to high toxicity; only 4a and 4d were nontoxic. The compound-mediated cytotoxicity assays showed that several pyrrole compounds demonstrated dose- and time-dependent cytotoxic activity against all tested tumor cell lines, the highest antitumor properties being achieved by 4a and its homologue 4d, especially against LoVo colon cells.

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Section: Resultssupporting

confidence: 91%

New Pyrrole Derivatives as Promising Biological Agents: Design, Synthesis, Characterization, In Silico, and Cytotoxicity Evaluation

Ivan

Bărbuceanu

Hotnog

et al. 2022

IJMS

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“…For better comparison with other in vitro toxicity endpoints (e.g., CHO cell cytotoxicity), Hep G2 cell cytotoxicity was examined for a wide spectrum of halogenated DBPs (including 31 cyclic and 12 aliphatic ones). Hep G2 is a human hepatoma cell line with well-differentiated cell, which retains many special functions of primary hepatocytes. , To date, the Hep G2 cell cytotoxicity assay has been applied to evaluate the toxicity of many substances, including chemicals, environmental pollutants, synthetic materials, and DBPs. − Procedures for the assay were basically according to previous studies and are described specifically in the Supporting Information (SI). , The conventional endpoint cytotoxicity assay CCK-8 was used to stain the microplate. When cell metabolism is normal, the reagent component WST-8 in CCK-8 could be reduced to highly water-soluble yellow-orange formazan products by dehydrogenase in cellular mitochondria.…”

Section: Methodsmentioning

confidence: 99%

“…34−36 Procedures for the assay were basically according to previous studies and are described specifically in the Supporting Information (SI). 36,37 The conventional endpoint cytotoxicity assay CCK-8 was used to stain the microplate. When cell metabolism is normal, the reagent component WST-8 in CCK-8 could be reduced to highly water-soluble yellow-orange formazan products by dehydrogenase in cellular mitochondria.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Comparative Toxicity Analyses from Different Endpoints: Are New Cyclic Disinfection Byproducts (DBPs) More Toxic than Common Aliphatic DBPs?

Wei

Luo

et al. 2021

Environ. Sci. Technol.

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In recent years, dozens of halogenated disinfection byproducts (DBPs) with cyclic structures were identified and detected in drinking water globally. Previous in vivo toxicity studies have shown that a few new cyclic DBPs possessed higher developmental toxicity and growth inhibition rate than common aliphatic DBPs; however, in vitro toxicity studies have proved that the latter exhibited higher cytotoxicity and genotoxicity than the former. Thus, to provide a more comprehensive toxicity comparison of DBPs from different endpoints, 11 groups of cyclic DBPs and nine groups of aliphatic DBPs were evaluated for their comparative in vitro and in vivo toxicity using human hepatoma cells (Hep G2) and zebrafish embryos. Notably, results showed that the in vitro Hep G2 cytotoxicity index of the aliphatic DBPs was nearly eight times higher than that of the cyclic DBPs, whereas the in vivo zebrafish embryo developmental/acute toxicity indexes of the cyclic DBPs were roughly 48–50 times higher than those of the aliphatic DBPs, indicating that the toxicity rank order differed when different endpoints were applied. For a broader comparison, a Pearson correlation analysis of DBP toxicity data from nine different endpoints was conducted. It was found that the observed Hep G2 cytotoxicity and zebrafish embryo developmental/acute toxicity in this study were highly correlated with the previously reported in vitro CHO cytotoxicity and in vivo toxicity in aquatic organisms (P < 0.01), respectively. However, the observed in vitro toxicity had no correlation with the in vivo toxicity (P > 0.05), suggesting that the toxicity rank orders obtained from in vitro and in vivo bioassays had large discrepancies. According to the observed toxicity data in this study and the candidate descriptors, two quantitative structure–activity relationship (QSAR) models were established, which help to further interpret the toxicity mechanisms of DBPs from different endpoints.

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“…Nonsteroidal anti-inflammatory drugs (NSAIDs) were the focus of another study by Qiu et al, who investigated DBP formation from chlorination. 161 Four indole-based NSAIDs were examined. Indomethacin and acemetacin underwent five types of reactions: chlorine substitution, hydrolysis, decarboxylation C−C coupling, and C−N cleavage; 19 DBPs were tentatively identified.…”

Section: ■ Pharmaceuticals and Hormonesmentioning

confidence: 99%

“…Nonsteroidal anti-inflammatory drugs (NSAIDs) were the focus of another study by Qiu et al, who investigated DBP formation from chlorination . Four indole-based NSAIDs were examined.…”

Section: Drinking Water and Swimming Pool Disinfection Byproductsmentioning

confidence: 99%

Water Analysis: Emerging Contaminants and Current Issues

2021

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Detection, transformation, and toxicity of indole-derivative nonsteroidal anti-inflammatory drugs during chlorine disinfection

Cited by 18 publications

References 45 publications

New Pyrrole Derivatives as Promising Biological Agents: Design, Synthesis, Characterization, In Silico, and Cytotoxicity Evaluation

New Pyrrole Derivatives as Promising Biological Agents: Design, Synthesis, Characterization, In Silico, and Cytotoxicity Evaluation

Comparative Toxicity Analyses from Different Endpoints: Are New Cyclic Disinfection Byproducts (DBPs) More Toxic than Common Aliphatic DBPs?

Water Analysis: Emerging Contaminants and Current Issues

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