Direct synthesis of 4-organylsulfenyl-7-chloro quinolines and their toxicological and pharmacological activities in Caenorhabditis elegans
| Autor: | Daniela De Freitas Câmara, Daiandra de Almeida Fagundez, Gelson Perin, Daiana Silva Ávila, Willian Goulart Salgueiro, Luis Fernando B. Duarte, Ana Thalita Gonçalves Soares, Diego Alves, Maurício C. D. F. Xavier |
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| Rok vydání: | 2014 |
| Předmět: |
Antioxidant
medicine.medical_treatment medicine.disease_cause Median lethal dose Antioxidants Superoxide dismutase chemistry.chemical_compound Paraquat Drug Discovery medicine Animals Caenorhabditis elegans Caenorhabditis elegans Proteins Pharmacology chemistry.chemical_classification Reactive oxygen species biology Superoxide Dismutase Superoxide Organic Chemistry Forkhead Transcription Factors General Medicine Oxidative Stress Biochemistry chemistry Catalase Quinolines biology.protein Reactive Oxygen Species Oxidative stress Signal Transduction Transcription Factors |
| Zdroj: | European Journal of Medicinal Chemistry. 75:448-459 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2014.01.037 |
| Popis: | We describe herein our results on the synthesis and biological properties in Caenorhabditis elegans of a range of 4-organylsulfenyl-7-chloroquinolines. This class of compounds have been easily synthesized in high yields by direct reaction of 4,7-dichloroquinoline with organylthiols using DMSO as solvent at room temperature under air atmosphere and tolerates a range of substituents in the organylsulfenyl moiety. We have performed a toxicological and pharmacological screening of the synthesized 4-organylsulfenyl-7-chloroquinolines in vivo in C. elegans acutely exposed to these compounds, under per se and stress conditions. Hence, we determined the lethal dose 50% (LD 50 ), in order to choose a nonlethal concentration (10 μM) and verified that at that concentration some of the compounds depicted protective action against the induced damage inflicted by paraquat, a superoxide generator. Two compounds ( 3c and 3h ) reduced the toxicity inflicted by paraquat above survival, reproduction and longevity of the worms, at least in part, by reducing the reactive oxygen species (ROS) generated by the toxicant exposure. Besides, these compounds increased the quantities of superoxide dismutase (SOD-3::GFP) and catalase (CTL-1,2,3::GFP), antioxidant enzymes. We concluded that the protective effects of the compounds observed in this study might have been a hormetic response dependent of the transcriptional factor DAF-16 / FOXO, causing a non-lethal oxidative stress that protects against the subsequently damage induced by paraquat. |
| Databáze: | OpenAIRE |
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