Theoretical study of the influence of spatial atomic arrangement in trypanocidal sesquiterpene lactones with high selectivity index

SÜLSEN V; FABIAN L.; FRANK F; CAZORLA S; FINKIELSZTEIN L; MARTINO V; MUSCHIETTI L; CATALAN C; MOGLIONI A

Ouro Preto

Simposio; The 5th Brazilian Symposium on Medicinal Chemistry; 2010

Sociedade Brasileira de Química

Chagas’s disease is one of the most important health problems throughout South America. It is caused by the intracellular protozoan Trypanosoma cruzi, which infects about 9–12 million people in Central and South America.1 Despite the progress made in the study of T. cruzi biochemistry and physiology2 in which several crucial enzymes, for parasite survival, have been identified as potential targets of new drugs, the chemotherapy to control this parasitic infection remains underdeveloped. The pharmacology is based on old and quite unspecific drugs associated with long term treatments that rise to severe side effects.3 In the search for new effective agents for the treatment of Chagas disease we have previously reported the in vitro and in vivo trypanocidal activity of sesquiterpene lactones (STLs) isolated from Argentine medicinal plants.4,5 Herein, we present the advances of a preliminary study of geometry optimization of a set of  12 STLs, with the aim to establish their structure activity relationship (SAR) as  trypanocidal agents.