Synthesis and biological evaluation in vitro and in silico of N-propionyl-N'-benzeneacylhydrazone derivatives as cruzain inhibitors of Trypanosoma cruzi.
Timoteo Delgado-MaldonadoBenjamín Nogueda-TorresJosé C Espinoza-HicksLenci K Vázquez-JiménezAlma D Paz-GonzálezAlfredo Juárez-SaldívarGildardo RiveraPublished in: Molecular diversity (2020)
An N-acylhydrazone scaffold has been used to develop new drugs with diverse biological activities, including trypanocidal activity against different strains of Trypanosoma cruzi. However, their mechanism of action is not clear, although in T. cruzi it has been suggested that the enzyme cruzain is involved. The aim in this work was to obtain new N-propionyl-N'-benzeneacylhydrazone derivatives as potential anti-T. cruzi agents and elucidate their potential mechanism of action by a molecular docking analysis and effects on the expression of the cruzain gene. Compounds 9 and 12 were the most active agents against epimastigotes and compound 5 showed better activity than benznidazole in T. cruzi blood trypomastigotes. Additionally, compounds 9 and 12 significantly increase the expression of the cruzain gene. In summary, the in silico and in vitro data presented herein suggest that compound 9 is a cruzain inhibitor.
Keyphrases
- trypanosoma cruzi
- molecular docking
- poor prognosis
- molecular dynamics simulations
- copy number
- genome wide
- genome wide identification
- human health
- dna methylation
- gene expression
- risk assessment
- transcription factor
- electronic health record
- machine learning
- big data
- deep learning
- artificial intelligence
- climate change