title: Synthesis and Antileishmanial Activity of Natural Dehydrodieugenol and Its Mono- and Dimethyl Ethers.
abstract: The study of chemistry of naturally occurring compounds and the synthesis of their derivatives is fundamentally important for the development of new drugs. In this work, dehydrodieugenol (DHDE) was obtained through oxidative coupling of eugenol, promoted by an aqueous mixture of potassium ferricyanide (K3 [Fe(CN)6 ]) and NH3  · H2 O. The partial methoxylation of DHDE with MeI and K2 CO3 mainly resulted in the molecular-shaped monomethyl ether (DHDE-1MeO) and its dimethyl ether derivative (DHDE-2MeO). The products from the reactions were characterized by (1) H- and (13) C-NMR spectroscopy. Additionally, these studies have reported the antileishmanial activity of DHDE against Leishmania amazonensis (IC50 value of 42.20 μg ml(-1) ) and shown that partial methoxylation of DHDE results in a significant increase in its antiparasitic activity (IC50 value of 13.68 μg ml(-1) ). Based on in vitro bioassays, DHDE-1MeO has shown the highest leishmanicidal activity in promastigota form. Production by direct one-step synthesis of this monomethoxylated compound can be considered to be a cost-effective and environmentally friendly method with a short reaction time.
authors.affiliation: Department of Biotechnology, Biotechnology Center, Federal University of Paraíba, Cidade Universitaria, João Pessoa, PB, 58051-970, Brazil.
authors.forename: Luis Cezar
authors.initials: LC
authors.lastname: Rodrigues
authors.affiliation: Department of Pharmaceutical Sciences, Biotechnology Center, Federal University of Paraíba, Cidade Universitaria, João Pessoa, PB, 58051-970, Brazil.
authors.forename: José Maria
authors.initials: JM
authors.lastname: Barbosa-Filho
authors.affiliation: Department of Molecular Biology, Federal University of Paraíba, Cidade Universitaria, João Pessoa, PB, 58051-970, Brazil.
authors.forename: Marcia Rosa
authors.initials: MR
authors.lastname: de Oliveira
authors.affiliation: Post-Graduate Program in Natural Products and Bioactives, Federal University of Paraíba, Cidade Universitaria, João Pessoa, PB, 58051-970, Brazil.
authors.forename: Patrícia Lima
authors.initials: PL
authors.lastname: do Nascimento Néris
authors.affiliation: Post-Graduate Program in Natural Products and Bioactives, Federal University of Paraíba, Cidade Universitaria, João Pessoa, PB, 58051-970, Brazil.
authors.forename: Flávio Valadares Pereira
authors.initials: FV
authors.lastname: Borges
authors.affiliation: Department of Biochemistry, Federal University of Pernambuco, Av. Prof. Moraes Rego, 1235 - Cidade Universitaria, Recife, PE, 50670-901, Brazil. robertomioso@yahoo.co.uk.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mioso
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005054:Eugenol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007891:Leishmania / Q000187:drug effects*; D017705:Lignans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008738:Methyl Ethers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D001688:Biological Products; D017705:Lignans; D008738:Methyl Ethers; C479487:dehydrodieugenol; D005054:Eugenol
keywords: Dehydrodieugenol; Eugenol dimer; Leishmanicidal activity; Lignans; Oxidative coupling