Vanessa Macedo, Ketlyn P da Motta, Carolina C Martins, Briana B Lemos, Allya Larroza, Roberto B Morais, Rodrigo K Steinhorst, Juliano A Roehrs, Diego Alves, Cristiane Luchese, Ethel Wilhelm
{"title":"7-氯-4-(苯基苯丙氨酰)喹啉的结构-活性关系:对小鼠的新型抗痛觉和抗炎作用","authors":"Vanessa Macedo, Ketlyn P da Motta, Carolina C Martins, Briana B Lemos, Allya Larroza, Roberto B Morais, Rodrigo K Steinhorst, Juliano A Roehrs, Diego Alves, Cristiane Luchese, Ethel Wilhelm","doi":"10.1002/cbdv.202301246","DOIUrl":null,"url":null,"abstract":"<p><p>The 7-chloro-4-(phenylselanyl)quinoline (4-PSQ) stands out for its potential antinociceptive and anti-inflammatory activities. Thus, in this study we investigated the structure-activity relationship of 4-PSQ and its analogues 7-chloro-4-[(4-fluorophenyl) selanyl]quinoline (a), 7-chloro-4-{[3-trifluoromethyl)phenyl] selanyl}quinoline (b), 4-((3,5-Bis(trifluoromethyl)phenyl)selanyl-7-chloroquinoline (c), 7-chloro-4-[(2,4,6-trimethyl)selanyl]quinolinic acid (d) and 7-chloroquinoline-4-selenium acid (e) in models of acute inflammation and chemical, thermal and mechanical nociception in mice, as well as by in silico methods. The compounds a (-F), b (-CF3), c (-Bis-CF3), d (-CH3), e (-OOH) and 4-PSQ exert antinociceptive effects in chemical and thermal nociception models, except compounds d (-CH3) and e (-OOH) that did not show antinociceptive effects in the hot plate test. In addition, treatments with all compounds did not cause locomotor changes in mice. In silico data the compounds revealed that only compound c (Bis-CF3) exhibited low gastrointestinal absorption and that compounds c (Bis-CF3) and e (-OOH) do not have the ability to penetrate the blood-brain barrier, indicating that compound e (-OOH) did not produce a central antinociceptive effect. Furthermore, we found that this class of compounds has a higher affinity for COX-2 than for COX-1. In general, our data indicate that the insertion of substituents can alter the efficiency of 4-PSQ as an antinociceptive and anti-inflammatory agent.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Structure-Activity Relationship of 7-Chloro-4-(Phenylselanyl) Quinoline: Novel Antinociceptive and Anti-Inflammatory Effects in Mice.\",\"authors\":\"Vanessa Macedo, Ketlyn P da Motta, Carolina C Martins, Briana B Lemos, Allya Larroza, Roberto B Morais, Rodrigo K Steinhorst, Juliano A Roehrs, Diego Alves, Cristiane Luchese, Ethel Wilhelm\",\"doi\":\"10.1002/cbdv.202301246\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The 7-chloro-4-(phenylselanyl)quinoline (4-PSQ) stands out for its potential antinociceptive and anti-inflammatory activities. 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In silico data the compounds revealed that only compound c (Bis-CF3) exhibited low gastrointestinal absorption and that compounds c (Bis-CF3) and e (-OOH) do not have the ability to penetrate the blood-brain barrier, indicating that compound e (-OOH) did not produce a central antinociceptive effect. Furthermore, we found that this class of compounds has a higher affinity for COX-2 than for COX-1. 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Structure-Activity Relationship of 7-Chloro-4-(Phenylselanyl) Quinoline: Novel Antinociceptive and Anti-Inflammatory Effects in Mice.
The 7-chloro-4-(phenylselanyl)quinoline (4-PSQ) stands out for its potential antinociceptive and anti-inflammatory activities. Thus, in this study we investigated the structure-activity relationship of 4-PSQ and its analogues 7-chloro-4-[(4-fluorophenyl) selanyl]quinoline (a), 7-chloro-4-{[3-trifluoromethyl)phenyl] selanyl}quinoline (b), 4-((3,5-Bis(trifluoromethyl)phenyl)selanyl-7-chloroquinoline (c), 7-chloro-4-[(2,4,6-trimethyl)selanyl]quinolinic acid (d) and 7-chloroquinoline-4-selenium acid (e) in models of acute inflammation and chemical, thermal and mechanical nociception in mice, as well as by in silico methods. The compounds a (-F), b (-CF3), c (-Bis-CF3), d (-CH3), e (-OOH) and 4-PSQ exert antinociceptive effects in chemical and thermal nociception models, except compounds d (-CH3) and e (-OOH) that did not show antinociceptive effects in the hot plate test. In addition, treatments with all compounds did not cause locomotor changes in mice. In silico data the compounds revealed that only compound c (Bis-CF3) exhibited low gastrointestinal absorption and that compounds c (Bis-CF3) and e (-OOH) do not have the ability to penetrate the blood-brain barrier, indicating that compound e (-OOH) did not produce a central antinociceptive effect. Furthermore, we found that this class of compounds has a higher affinity for COX-2 than for COX-1. In general, our data indicate that the insertion of substituents can alter the efficiency of 4-PSQ as an antinociceptive and anti-inflammatory agent.
期刊介绍:
Chemistry & Biodiversity serves as a high-quality publishing forum covering a wide range of biorelevant topics for a truly international audience. This journal publishes both field-specific and interdisciplinary contributions on all aspects of biologically relevant chemistry research in the form of full-length original papers, short communications, invited reviews, and commentaries. It covers all research fields straddling the border between the chemical and biological sciences, with the ultimate goal of broadening our understanding of how nature works at a molecular level.
Since 2017, Chemistry & Biodiversity is published in an online-only format.