Synthesis and leishmanicidal activity of eugenol derivatives bearing 1,2,3-triazole functionalities.

Autor: Teixeira RR; Departamento de Química, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, Viçosa, MG, 36570-900, Brazil. Electronic address: robsonr.teixeira@ufv.br., Gazolla PAR; Departamento de Química, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, Viçosa, MG, 36570-900, Brazil., da Silva AM; Instituto Federal de Educação, Ciência e Tecnologia Catarinense, Campus Araquari Rodovia BR 280, Km 27, Cx. Postal 21, Araquari, SC, 89245-000, Brazil., Borsodi MPG; Instituto de Biofísica Carlos Chagas Filho, Laboratório de Imunofarmacologia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco I2-038, Ilha do Fundão, Rio de Janeiro, 21941-902, RJ, Brazil., Bergmann BR; Instituto de Biofísica Carlos Chagas Filho, Laboratório de Imunofarmacologia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco I2-038, Ilha do Fundão, Rio de Janeiro, 21941-902, RJ, Brazil., Ferreira RS; Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Belo Horizonte, 31270-901, MG, Brazil., Vaz BG; Instituto de Química, Universidade Federal de Goiás, Av. Esperança, S/N, Campus Samambaia, Goiânia, 74690-970, GO, Brazil., Vasconcelos GA; Instituto de Química, Universidade Federal de Goiás, Av. Esperança, S/N, Campus Samambaia, Goiânia, 74690-970, GO, Brazil., Lima WP; Instituto de Biofísica Carlos Chagas Filho, Laboratório de Imunofarmacologia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco I2-038, Ilha do Fundão, Rio de Janeiro, 21941-902, RJ, Brazil.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2018 Feb 25; Vol. 146, pp. 274-286. Date of Electronic Publication: 2018 Feb 04.
DOI: 10.1016/j.ejmech.2018.01.046
Abstrakt: In this paper, it is described the synthesis and the evaluation of the leishmanicidal activity of twenty-six eugenol derivatives bearing 1,2,3-triazole functionalities. The evaluation of the compounds on promastigotes of Leishmania amazonensis (WHOM/BR/75/Josefa) showed that eugenol derivatives present leishmanicidal activities with varying degrees of effectiveness. The most active compound, namely 4-(3-(4-allyl-2-methoxyphenoxy)propyl)-1-(4-methylbenzyl)-1H-1,2,3-triazole (7k) (IC 50  = 7.4 ± 0.8 μmol L -1 ), also targeted Leishmania parasites inside peritoneal macrophages (IC 50  = 1.6 μmol L -1 ) without interfering with cell viability. The cytotoxicity of 7k against macrophage cells presented IC 50 of 211.9 μmol L -1 and the selective index was equal to 132.5. Under similar conditions, compound 7k was more effective than glucantime and pentamidine, two drugs currently in the clinic. In addition, theoretical calculations showed that this compound also presents most physicochemical and pharmacokinetic properties within the ranges expected for orally available drugs. It is believed that eugenol bearing 1,2,3-triazole functionalities may represent a scaffold to be explored toward the development of new agents to treat leishmaniasis.
(Copyright © 2018 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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