9Th Brazilian Symposium on Medicinal Chemistry

Myeloperoxidase (MPO) is an oxyreductase enzyme producing reactive species that play a key role in
neutrophil antimicrobial activity. 1 HOCl is the most abundant and important product of MPO, it can chlorinate
biomolecules including proteins, lipids, and nucleic acids at the site of inflammation. MPO is involved in a
growing number of diseases like inflammatory conditions, neurodegenerative diseases, cystic fibrosis, asthma,
atherosclerosis and cancer 2 . Thus, the development of therapeutic strategies for MPO inhibition is increasingly
necessary. This work aims the design, synthesis and pharmacological evaluation of hydrazides derivatives as
MPO inhibitors candidates. In vitro evaluation was performed against MPO-dependent HOCl production
showing that hydrazide derivatives promising good inhibitors of enzymatic activity. 3 The derivative 1a was the
most potent with IC 50 value of 0,15 ± 0,03 μM. In silico studies of docking and molecular dynamics allowed the
proposition of molecular binding modes.