Synthesis, antileishmanial activity and mechanism of action studies of novel β-carboline-1,3,5-triazine hybrids
| Autor: | Paula Baréa, Maria Helena Sarragiotto, Celso Vataru Nakamura, Willian Ferreira da Costa, Danielle Lazarin Bidóia, Valéria Aquilino Barbosa, Jéssica Carreira de Paula, Talitha Fernandes Stefanello |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Programmed cell death Antiprotozoal Agents 01 natural sciences Cell Line Mice Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Parasitic Sensitivity Tests 1 3 5-Triazine Drug Discovery medicine Animals Structure–activity relationship Amastigote Axenic Leishmania Pharmacology Cell Death Dose-Response Relationship Drug Molecular Structure biology Triazines 010405 organic chemistry Chemistry Macrophages Organic Chemistry General Medicine biology.organism_classification 0104 chemical sciences 030104 developmental biology Mechanism of action Biochemistry Cell culture medicine.symptom Carbolines |
| Zdroj: | European Journal of Medicinal Chemistry. 150:579-590 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2018.03.014 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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