title: Direct synthesis of 4-organylsulfenyl-7-chloro quinolines and their toxicological and pharmacological activities in Caenorhabditis elegans.
abstract: 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.
authors.affiliation: Grupo de Pesquisa em Bioquímica e Toxicologia em Caenorhabditis elegans (GBToxCE), Universidade Federal do Pampa-UNIPAMPA, BR 592, Km 472, CEP 97500-970 Uruguaiana, RS, Brazil.
authors.forename: Willian G
authors.initials: WG
authors.lastname: Salgueiro
authors.affiliation: Laboratório de Síntese Orgânica Limpa - LASOL - CCQFA - Universidade Federal de Pelotas - UFPel, CEP 96010-900 Pelotas, RS, Brazil.
authors.forename: Maurício C D F
authors.initials: MC
authors.lastname: Xavier
authors.affiliation: Laboratório de Síntese Orgânica Limpa - LASOL - CCQFA - Universidade Federal de Pelotas - UFPel, CEP 96010-900 Pelotas, RS, Brazil.
authors.forename: Luis Fernando B
authors.initials: LF
authors.lastname: Duarte
authors.affiliation: Grupo de Pesquisa em Bioquímica e Toxicologia em Caenorhabditis elegans (GBToxCE), Universidade Federal do Pampa-UNIPAMPA, BR 592, Km 472, CEP 97500-970 Uruguaiana, RS, Brazil.
authors.forename: Daniela F
authors.initials: DF
authors.lastname: Câmara
authors.affiliation: Grupo de Pesquisa em Bioquímica e Toxicologia em Caenorhabditis elegans (GBToxCE), Universidade Federal do Pampa-UNIPAMPA, BR 592, Km 472, CEP 97500-970 Uruguaiana, RS, Brazil.
authors.forename: Daiandra A
authors.initials: DA
authors.lastname: Fagundez
authors.affiliation: Grupo de Pesquisa em Bioquímica e Toxicologia em Caenorhabditis elegans (GBToxCE), Universidade Federal do Pampa-UNIPAMPA, BR 592, Km 472, CEP 97500-970 Uruguaiana, RS, Brazil.
authors.forename: Ana Thalita G
authors.initials: AT
authors.lastname: Soares
authors.affiliation: Laboratório de Síntese Orgânica Limpa - LASOL - CCQFA - Universidade Federal de Pelotas - UFPel, CEP 96010-900 Pelotas, RS, Brazil.
authors.forename: Gelson
authors.initials: G
authors.lastname: Perin
authors.affiliation: Laboratório de Síntese Orgânica Limpa - LASOL - CCQFA - Universidade Federal de Pelotas - UFPel, CEP 96010-900 Pelotas, RS, Brazil. Electronic address: diego.alves@ufpel.edu.br.
authors.forename: Diego
authors.initials: D
authors.lastname: Alves
authors.affiliation: Grupo de Pesquisa em Bioquímica e Toxicologia em Caenorhabditis elegans (GBToxCE), Universidade Federal do Pampa-UNIPAMPA, BR 592, Km 472, CEP 97500-970 Uruguaiana, RS, Brazil. Electronic address: avilads1@gmail.com.
authors.forename: Daiana Silva
authors.initials: DS
authors.lastname: Avila
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D051858:Forkhead Transcription Factors; D018384:Oxidative Stress / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000975:Antioxidants; D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D011804:Quinolines; D017382:Reactive Oxygen Species; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C035317:4,7-dichloroquinoline; D013482:Superoxide Dismutase
keywords: Antioxidants; Caenorhabditis elegans; Hormesis; Quinolines; Sulfur