Synthesis, antileishmanial activity and mechanism of action studies of novel β-carboline-1,3,5-triazine hybrids.

Autor: Baréa P; Universidade Estadual de Maringá (UEM), Departamento de Química, Av. Colombo, 5790, CEP: 87020-900, Maringá, PR, Brazil., Barbosa VA; Universidade Estadual de Maringá (UEM), Departamento de Química, Av. Colombo, 5790, CEP: 87020-900, Maringá, PR, Brazil., Bidóia DL; Universidade Estadual de Maringá (UEM), Departamento de Análises Clínicas, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP: 87020-900, Maringá, PR, Brazil., de Paula JC; Universidade Estadual de Maringá (UEM), Departamento de Análises Clínicas, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP: 87020-900, Maringá, PR, Brazil., Stefanello TF; Universidade Estadual de Maringá (UEM), Departamento de Análises Clínicas, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP: 87020-900, Maringá, PR, Brazil., da Costa WF; Universidade Estadual de Maringá (UEM), Departamento de Química, Av. Colombo, 5790, CEP: 87020-900, Maringá, PR, Brazil., Nakamura CV; Universidade Estadual de Maringá (UEM), Departamento de Análises Clínicas, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP: 87020-900, Maringá, PR, Brazil., Sarragiotto MH; Universidade Estadual de Maringá (UEM), Departamento de Química, Av. Colombo, 5790, CEP: 87020-900, Maringá, PR, Brazil. Electronic address: mhsarragiotto@uem.br.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2018 Apr 25; Vol. 150, pp. 579-590. Date of Electronic Publication: 2018 Mar 06.
DOI: 10.1016/j.ejmech.2018.03.014
Abstrakt: A series of novel hybrids β-carboline-1,3,5-triazine were synthesized and evaluated for their in vitro antileishmanial activity against promastigote and amastigote forms of Leishmania amazonensis. Among the compounds tested, the hybrids 9d, 9e, 16a and 16b showed potent activity against the promastigote forms with IC 50 values less than 8 μM. Compounds 9e and 16b were also active against amastigote forms, displaying IC 50 values of 1.0 ± 0.1 μM and 1.2 ± 0.5 μM, respectively. Besides that, the hybrid 16b bearing the 4-methoxyphenyl group at C-1 of β-carboline and isopropylamino group at 1,3,5-triazine, showed low toxicity, being 23.5 and 121.4 times more toxic for promastigotes and axenic amastigotes, respectively, than for macrophage J774-A1 cell lines. Investigation of action mechanism in promastigotes showed that compound 16b caused alterations in cell division cycle and an increase of lipid-storage bodies, leading the cells to death through various factors. The accumulation of lipid bodies may be associated with apoptotic cell death.
(Copyright © 2018 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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