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

Basic Information

ID: ALA4145511

Journal: Eur J Med Chem

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

Authors: Teixeira RR, Gazolla PAR, da Silva AM, Borsodi MPG, Bergmann BR, Ferreira RS, Vaz BG, Vasconcelos GA, Lima WP.

Abstract: 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) (IC50 = 7.4 ± 0.8 μmol L-1), also targeted Leishmania parasites inside peritoneal macrophages (IC50 = 1.6 μmol L-1) without interfering with cell viability. The cytotoxicity of 7k against macrophage cells presented IC50 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.

CiteXplore: 29407957

DOI: 10.1016/j.ejmech.2018.01.046

Patent ID: ┄