Docking study of the sesquiterpene lactone cumanin and its derivatives on Trypanothione reductase from Trypanosoma cruzi

FABIAN L.; MOGLIONI A; BORGO J; SÜLSEN V; BEER MF; DONADEL O

CABA

Congreso; XI Congreso Argentino de Protozoología y Enfermedades Parasitarias. 1era Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedades de Biociencias

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is endemic in Latin America. Trypanothione reductase (TcTR) is an enzyme critical in maintaining the thiol redox balance in trypanosomatids. That is why it is one of the most important antichagasic drug target. Based on the experimental evidence of the trypanosomicidal activity of the sesquiterpene lactone cumanin, acquired by this working group and reported in the literature1, several derivatives were obtained from it. The use of docking methods to identify potential candidates is a valuable tool extensively used for evaluating compounds and for guiding the synthesis of derivatives. On the basis of the knowledge of the biological target and its crystallography (PDB: 1GXF), and having already validated docking protocols2, we have developed an hybrid method of DOCKING / QSAR3D, to study cumanin and its derivatives in order to have a theoretical evaluation protocol to estimate their potential as TcTR inhibitors. The best estimate of activity has been determined.The hybrid method let us to identify cumanin and its derivatives as good inhibitors of TcTR, making them promising lead compounds. Based on these promising results and the estimates for the derivatives, the biological assays will be carried out.