title: Design, synthesis and trypanocidal evaluation of novel 1,2,4-triazoles-3-thiones derived from natural piperine.
abstract: The work reported herein describes the synthesis and the assessment of the trypanocidal activity of thirteen new 1,2,4-triazole-3-thiones obtained from natural piperine, the main constituent of the dry fruits of Piper nigrum. It is part of a research program aiming to use abundant and easily available natural products as starting materials for the design and synthesis of new molecules potentially useful as antiparasitic drugs. The variously substituted triazole derivatives were synthesized from the natural amide in four steps with the use of microwave irradiation on overall yields ranging from 32% to 51%. The cyclohexyl substituted derivative showed the best trypanocidal profile on proliferative forms of Trypanosoma cruzi (Y strain), with IC₅₀s = 18.3 and 8.87 mM against epimastigotes and amastigotes, respectively.
authors.affiliation: Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Rural do Rio de Janeiro, BR 465, Km 07, CEP: 23.890-000, Seropédica, RJ, Brazil.
authors.forename: Tatiany Nunes
authors.initials: TN
authors.lastname: Franklim
authors.forename: Leonardo
authors.initials: L
authors.lastname: Freire-de-Lima
authors.forename: Julliana
authors.initials: J
authors.lastname: de Nazareth Sá Diniz
authors.forename: José Osvaldo
authors.initials: JO
authors.lastname: Previato
authors.forename: Rosane Nora
authors.initials: RN
authors.lastname: Castro
authors.forename: Lucia
authors.initials: L
authors.lastname: Mendonça-Previato
authors.forename: Marco Edilson Freire
authors.initials: ME
authors.lastname: de Lima
mesh_terms: D000470:Alkaloids / Q000737:chemistry*; D052117:Benzodioxoles / Q000737:chemistry*; D015195:Drug Design; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010880:Piperidines / Q000737:chemistry*; D053284:Polyunsaturated Alkamides / Q000737:chemistry*; D013871:Thiones / Q000138:chemical synthesis / Q000737:chemistry*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D013871:Thiones; D014230:Triazoles; D014344:Trypanocidal Agents; C045575:1,2,4-triazole; C008922:piperine