CRUZIPAIN INHIBITION BY THIOSEMICARBAZONES: STRUCTURAL DETERMINANTS OF THEIR ACTIVITY.

GABRIEL J. JASINSKI ; LUCAS E. FABIAN; ALBERTINA G. MOGLIONI

Simposio; Drug Discovery for Neglected Diseases International Congress 2018; 2018

Chagas disease is an endemic tripanosomiasis in the Americas, affecting almost 10 million people, with 70 million at risk of contracting the disease.1 The current therapy is based on the administration of drugs such as nifurtimox and benznidazole, which a have limited efficacy and can lead to serious adverse effects. Therefore, the development of new compounds with effective and safe action is essential. In this context, cruzipain (a key cysteine-protease in the life cycle of the parasite) is an especially interesting target for drug design and have been shown tha thiosemicarbazone compounds have a marked anti-cruzipain activity. It has been established that the factors of distribution of molecular mass and the accessible surface of low polarity are important structural characteristics for the anti-cruzain activity of thiosemicarbazones. The predictive models of 3D-QSAR type proposed in this paper are applicable in ligand optimization and virtual screening schemes.