Structure-trypanocidal activity relationship of natural sesquiterpene lactones from Argentine Asteraceae species

FABIAN L , CAZORLA S., SÜLSEN V , CATALÁN C, FINKIELSTEIN L, MARTINO V , MUSCHIETTI L, FRANK F, MOGLIONI A

Berlin,

Congreso; 58th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research,; 2010

Society for Medicinal Plant and Natural Product Research

Based on our previous findings of sesquiterpene lactones (STLs) with antiprotozoal activity, against Trypanosoma cruzi and Leishmaniasp., from the genus Ambrosia(1), we now report the structure- trypanocidal activity relationship on natural STLs from Argentine Asteraceae species.The trypanocidal activity of a set of 20 STLs from different types was measured on T. cruzi epimastigotes by the H-thymidine uptake technique (1). The 50% inhibitory concentration (IC50) values of the assayed STLs was in the range of 0.06 to 17.97 μg/ml. Estafietin, psilostachyin, eupahakonenin, enhydrin and parthenolide were the most active compounds with IC>50 values below 1μg/ml. All the STLs assayed were included in a structure-activity relationship study (SAR) and were divided into two groups: Group I, including STLs with IC50 1μg/ml and group II STLs with IC50 10 μg/ml. Molecule geometry was optimized using a Gaussian 03W version 6.0 program. Physicochemical parameters were calculated and mathematically correlated with the obtained IC50 values. Results of the trypanocidal activity of the assayed STLs and the graphical superposition of compounds of groups I and II and within each group will be presented.