Development of a new fluorine-containing benzothizole as novel trypanocidal agent: Design, in silico study and their in vitro and in vivo activity evaluation

4^th International Conference on Medicinal Chemistry & Computer Aided Drug Designing

November 02-04, 2015 Atlanta, USA

Roberto I Cuevas-Hern�?¡ndez

Instituto Polit�?©cnico Nacional, Mexico

Posters-Accepted Abstracts: Med chem

Abstract :

Trypanosoma cruzi (T. cruzi) is the causal agent of Chagas disease. In the human host, trypomastigote phase depends on the route of glycolysis. Also, Triosephosphate Isomerase (TIM) is important enzyme for the optimal functioning of this metabolic pathway. In the present study, 207 benzazoles were designed and evaluated in silico as TcTIM inhibitors. Five molecules were synthesized and their trypanocidal activity was tested in vitro. The most active compound was evaluated in vivo in the short term, we calculate the LD50 and some biochemical parameters to estimate its hepatotoxicity. The docking results showed that all compounds have affinity to the aromatic cluster of the TcTIM interface, with important electrostatic, hydrophobic and Ï�?-Ï�? interactions. The benzothiazole derivatives showed better physicochemical attributes (including non toxicity) and the QSAR study indicates that the inhibition of TcTIM improves when the compounds are substituted with hyper-conjugated systems and when there is a sulfur atom in their structure like benzothiazole. The in vitro results showed that the agent, fluorine-containing benzothizole, called BT3 is better than benznidazole from 62.5 �?¼g/mL, treatment in vivo showed that is not enough a single oral administration to stop the parasitemia. Finally, the biochemical parameters suggest that the new synthesized compound does not produce liver damage in repeated doses for 21 days; so it is suggested to explore another route of administration and implement a long-term therapy to treat Chagas with this novel compound.

Biography :

Email: rcuevash@ipn.mx