Direct synthesis of 4-organylsulfenyl-7-chloro quinolines and their toxicological and pharmacological activities in Caenorhabditis elegans

• Published in: European journal of medicinal chemistry Vol. 75; pp. 448 - 459
• Main Authors: Salgueiro, Willian G., Xavier, Maurício C.D.F., Duarte, Luis Fernando B., Câmara, Daniela F., Fagundez, Daiandra A., Soares, Ana Thalita G., Perin, Gelson, Alves, Diego, Avila, Daiana Silva
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 21.03.2014; Elsevier
• Subjects: Animals; Antioxidants; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Antioxidants - toxicity; Caenorhabditis elegans; Caenorhabditis elegans - drug effects; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - metabolism; Chemistry, Medicinal; Forkhead Transcription Factors; Hormesis; Life Sciences & Biomedicine; Oxidative Stress - drug effects; Pharmacology & Pharmacy; Quinolines; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - pharmacology; Quinolines - toxicity; Reactive Oxygen Species - metabolism; Science & Technology; Signal Transduction - drug effects; Sulfur; Superoxide Dismutase - metabolism; Transcription Factors - metabolism; Quinolines; Antioxidants; Caenorhabditis elegans; Hormesis; Sulfur; OXIDATIVE STRESS; TOXICITY; DAMAGE; LIFE-SPAN EXTENSION; ANTIOXIDANT; DAF-16; THIOREDOXIN REDUCTASE; HYDROGEN-PEROXIDE; ORGANOTELLURIUM; SUPEROXIDE-DISMUTASE
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.01.037

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% (LD50), 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. [Display omitted] •Sulfur-containing quinolines were directly synthesized under mild reaction conditions.•Compounds attenuated the oxidative damage on survival, reproduction and longevity through a hormetic response.•Compounds modulated the DAF-16/FOXO pathway.•DAF-16/FOXO modulation possibly up-regulated SOD-3::GFP and CTL-1,2::GFP lowering the ROS levels.