Synthesis of methylidene-1-tetralone derivatives with potential anti-chagasic activity

The American trypanosomiasis known as Chagas disease (CD) has been recognized by the WHO as one of the 13 most neglected tropical diseases in the world and by PAHO as a disease of poverty, representing a relevant social and economic problem in many countries of Latin America.This research work describes the synthesis and chemical characterization of new compounds derived from methylidene-1-tetralone analogs and their possible anti-chagasic activity. Intermediates3-6 were generated through simple nucleophilic substitution of 2-chloropyridine-3-carbaldehyde with 4-halophenol respective. Final compounds 7-22 were generated through a Claisen-Schmidt cross aldol condensation between 3-6 and the 1-tetralone respective. Biological evaluation was performed in vitro on the viability of T. cruziepimastigotes, VERO and MBDM cell lines using the MTT method. Compounds 19 – 22 showed an inhibitory effect on the growth of T. cruziepimastigotes, however, compounds21 and 22 showed a marked inhibitory effect on the growth of T. cruzi, even proving to be more active than beznidazole (Bnz)used as referencedrug.Thisstudy shows theimportanceofmethylidene-1-tetralone derivatives as an alternative treatment for this specie, which is the most important from the epidemiological point of viewin America.