title: Synthesis and biological evaluation of novel piperidine-benzodioxole derivatives designed as potential leishmanicidal drug candidates.
abstract: A novel series of ester and carbamate derivatives was synthesized and evaluated its activities against Leishmania amazonensis. All compounds exhibited weaker leishmanicidal activity than amphotericin B. However, results indicated that substituents on the aryl-acyl subunit are important for modulation of the leishmanicidal effect. The nitro derivative showed the highest activity of the series with an IC50 = 17.24 μM, and comparable potency to the 3,4-benzodioxole ester and n-hexyl carbamate derivatives. All compounds showed low toxicity against human cells. These results revealed interesting novel piperine-like molecular pattern for exploitation in search and development of effective and low toxic antileishmanial drug candidates.
authors.affiliation: LFQM-Laboratório de Fitoquímica e Química Medicinal, Institute of Chemistry, Federal University of Alfenas, Alfenas, MG 37130-000, Brazil; PPGCF-Programa de Pós-Graduação em Ciências Farmacêuticas, Federal University of Alfenas, Alfenas, MG 37130-000, Brazil.
authors.forename: Ítalo A
authors.initials: ÍA
authors.lastname: Fernandes
authors.affiliation: Laboratório de Biologia Molecular de Microrganismos, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, MG 37130-000, Brazil.
authors.forename: Letícia
authors.initials: L
authors.lastname: de Almeida
authors.affiliation: Laboratório de Biologia Molecular de Microrganismos, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, MG 37130-000, Brazil.
authors.forename: Patrícia Espuri
authors.initials: PE
authors.lastname: Ferreira
authors.affiliation: Laboratório de Biologia Molecular de Microrganismos, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, MG 37130-000, Brazil.
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: Marques
authors.affiliation: Laboratório de Vacinas, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, MG 37130-000, Brazil.
authors.forename: Raíssa P
authors.initials: RP
authors.lastname: Rocha
authors.affiliation: Laboratório de Vacinas, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, MG 37130-000, Brazil.
authors.forename: Luiz F L
authors.initials: LF
authors.lastname: Coelho
authors.affiliation: LQFAR-Laboratório de Pesquisa em Química Farmacêutica, Department of Food and Medicines, Federal University of Alfenas, Alfenas, MG 37130-000, Brazil.
authors.forename: Diogo T
authors.initials: DT
authors.lastname: Carvalho
authors.affiliation: LFQM-Laboratório de Fitoquímica e Química Medicinal, Institute of Chemistry, Federal University of Alfenas, Alfenas, MG 37130-000, Brazil; PPGCF-Programa de Pós-Graduação em Ciências Farmacêuticas, Federal University of Alfenas, Alfenas, MG 37130-000, Brazil. Electronic address: cvjviegas@gmail.com.
authors.forename: Claudio
authors.initials: C
authors.lastname: Viegas
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D052117:Benzodioxoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery; D006801:Humans; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects*; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D052117:Benzodioxoles; D010880:Piperidines; C032727:piperidine
keywords: Leishmania amazonensis; Leishmaniasis; Leishmanicidal activity; Medicinal chemistry; Piperine