6533b862fe1ef96bd12c6c80
RESEARCH PRODUCT
Novel [1,2,3]triazolo[1,5-a]pyridine derivatives are trypanocidal by sterol biosynthesis pathway alteration.
Mauricio Moncada-basualtoMauricio Moncada-basualtoMichel LapierBenjamín Aguilera-venegasFabiola González-herreraClaudio Olea-azarBelén AbarcaRafael Ballesteros-garridoUlrike KemmerlingBarbara PesceJuan Diego MayaRafael BallesterosDaniela Guzmán-riverasubject
Cell cycle checkpointPyridinesTrypanosoma cruziSterol Biosynthesis Pathway01 natural sciences03 medical and health scienceschemistry.chemical_compoundMiceDrug DiscoveryPyridineAnimalsHumansPharmacologic therapyChagas Disease030304 developmental biologyTrypanocidal agentPharmacology0303 health sciencesCell CycleTriazolesTrypanocidal Agents0104 chemical sciencesBiosynthetic Pathways010404 medicinal & biomolecular chemistrySterolsRAW 264.7 CellsBiochemistrychemistryMolecular Medicinedescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-05-01 | Future medicinal chemistry |