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

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

  • Eur J Med Chem. 2018 Apr 25:150:579-590. doi: 10.1016/j.ejmech.2018.03.014.
Paula Baréa 1,  Valéria Aquilino Barbosa 1,  Danielle Lazarin Bidóia 2,  Jéssica Carreira de Paula 2,  Talitha Fernandes Stefanello 2,  Willian Ferreira da Costa 1,  Celso Vataru Nakamura 2,  Maria Helena Sarragiotto 3
Affiliations

Affiliations

  • 1 Universidade Estadual de Maringá (UEM), Departamento de Química, Av. Colombo, 5790, CEP: 87020-900, Maringá, PR, Brazil.
  • 2 Universidade Estadual de Maringá (UEM), Departamento de Análises Clínicas, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP: 87020-900, Maringá, PR, Brazil.
  • 3 Universidade Estadual de Maringá (UEM), Departamento de Química, Av. Colombo, 5790, CEP: 87020-900, Maringá, PR, Brazil. Electronic address: mhsarragiotto@uem.br.
PMID: 29549842 DOI: 10.1016/j.ejmech.2018.03.014
Abstract

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 IC50 values less than 8 μM. Compounds 9e and 16b were also active against amastigote forms, displaying IC50 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.

Keywords

1,3,5-Triazine; Antileishmanial; Cell death mechanism; Leishmania amazonensis; β-carboline.

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