Journal of Clinical & Experimental Pharmacology

Design, synthesis and biological evaluation of hybrid bioisoster derivatives of hydrazone and nitric oxide releasing groups with potential and selective anti-Trypanosoma cruzi activity

3^rd World Congress on Pharmacology

August 08-10, 2016 Birmingham, UK

Ricardo Augusto Massarico Serafim

University of Sao Paulo, Brazil

Posters & Accepted Abstracts: Clin Exp Pharmacol

Abstract:

Hybrid bioisoster derivatives from N-acylhydrazones and furoxan groups were designed with the objective of obtaining at least a dual mechanism of action: cruzain inhibition and nitric oxide (NO) releasing activity. Fifteen designed compounds were synthesized varying the substitution in N-acylhydrazone and in furoxan group as well. They had its anti-Trypanosoma cruzi activity in amastigotes forms, NO releasing potential and inhibitory cruzain activity evaluated. The two most active compounds both in the parasite amastigotes and in the enzyme contain the nitro group in para position of the aromatic ring. The permeability screening in Caco-2 cell and cytotoxicity assay in human cells were performed for those most active compounds and both showed to be less cytotoxic than the reference drug, benznidazole. Also molecular modeling approach was used to find the molecular properties that more influenced the biological activity and to evaluate the interaction with the molecular target cruzain. Compound containing nitro group in para position was the most promising, since besides activity it showed good permeability, selectivity index, higher than the reference drug and also showed no significant changes in human cells in studies of DNA fragmentation and cell cycle. Thereby this compound was considered a promising compound for further in vivo studies. Nevertheless optimization in its structure has been carry out to improve the pharmacodynamics and pharmacokinetics properties.

Biography :

Email: ramserafim@gmail.com