Novel [1,2,3]triazolo[1,5-a]pyridine derivatives are trypanocidal by sterol biosynthesis pathway alteration
| Autor: | Mauricio Moncada-Basualto, Michel Lapier, Benjamín Aguilera-Venegas, Fabiola González-Herrera, Claudio Olea-Azar, Belén Abarca, Rafael Ballesteros-Garrido, Ulrike Kemmerling, Barbara Pesce, Juan Diego Maya, Rafael Ballesteros, Daniela Guzmán-Rivera |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Cell cycle checkpoint
Pyridines Trypanosoma cruzi Sterol Biosynthesis Pathway 01 natural sciences 03 medical and health sciences chemistry.chemical_compound Mice Drug Discovery Pyridine Animals Humans Pharmacologic therapy Chagas Disease 030304 developmental biology Trypanocidal agent Pharmacology 0303 health sciences Cell Cycle Triazoles Trypanocidal Agents 0104 chemical sciences Biosynthetic Pathways 010404 medicinal & biomolecular chemistry Sterols RAW 264.7 Cells Biochemistry chemistry Molecular Medicine |
| Zdroj: | Future medicinal chemistry. 11(10) |
| ISSN: | 1756-8927 |
| Popis: | Aim: To study a new series of [1,2,3]triazolo[1,5-α]pyridine derivatives as trypanocidal agents because current antichagasic pharmacologic therapy is only partially effective. Materials & methods: The effect of the series upon Trypanosoma cruzi epimastigotes and murine macrophages viability, cell cycle, cell death and on the metabolites of the sterol biosynthesis pathway was measured; also, docking in 14α-demethylase was analyzed. Results: Compound 16 inhibits 14α-demethylase producing an imbalance in the cholesterol/ergosterol synthesis pathway, as suggested by a metabolic control and theoretical docking analysis. Consequently, it prevented cell proliferation, stopping the cellular cycle at the G2/M phase, inducing cell death. Conclusion: Although the exact cell death mechanism remained elusive, this series can be used for the further rational design of novel antiparasitic molecules. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|