9Th Brazilian Symposium on Medicinal Chemistry

Chagas’ disease is a tropical neglected disease caused by Trypanosoma cruzi. Based on natural 4-alkylphenols, LINS03 series was designed, proposing analogues with different substituents on the aromatic ring and functionalized alkyl chain.1 Exploratory data analysis suggested that the most active analogues, esters and amides (EC50 20.1 to >100 µM) and amines (EC50 1.33-13.3 µM), are separated by higher being more hydrosoluble.2 To enhance the hydrosolubility, 5 new meta-substituted analogues (OMe or OH), were tested. Amines 1-3 were inactive against the amastigotes (EC50>100 µM) and were cytotoxic. Esters 4 and 5, had an improved activity (EC50 6.8 and 13.9 µM) and selectivity (18.2 and 7.7) against the amastigotes, respectively.3 Different correlations exist for the activity of the basic (amines) and neutral analogues following the addition of a new substituent in meta, suggesting that for a compound to be significantly active (EC50<10 µM) it must be in an ideal range of hydrosolubility.