anti- activity enhancement of curcumin by its monoketone tetramethoxy analog diveratralacetone.

Chagas disease is a tropical disease caused by the protozoan parasite and currently affects millions of people worldwide. Curcumin (CUR), the major constituent of turmeric spice (dry powder of L. plant rhizomes and roots), exhibits antiparasitic activity against protozoan parasites . However, because of its chemical instability, poor cellular uptake and limited bioavailability it is not suitable for clinical use. The objective of this study was to synthesize and evaluate CUR monoketone analog dibenzalacetone (DBA ) and its non-phenolic, methoxy () and chloro () derivatives for better stability and bioavailability against . Diveratralacetone, the tetramethoxy DBA (DBA ), was found to be the CUR analog with most enhanced activity against the amastigote forms of four strains of tested (Brazil, CA-I/72, Sylvio X10/4 and Sylvio X10/7) with 50% inhibitory concentration (IC) < 10 μM (1.51-9.63 μM) and selectivity index (SI) > 10 (C2C12 non-infected mammalian cells). This was supplemented by time-course assessment of its anti- activity. DBA and its dimethoxy (DBA ) and hexamethoxy (DBA ) derivatives were substantially less active. The inactivity of dichloro-DBA (DBA ) was indicative of the important role played by oxygenated groups such as methoxy in the terminal aromatic rings in the DBA molecule, particularly at position to form reactive oxygen species essential for anti- activity. Although the DBAs and CUR were toxic to infected mammalian cells , in a mouse model, both DBA and CUR did not exhibit acute toxicity or mortality. These results justify further optimization and anti- activity evaluation of the inexpensive diveratralacetone for its potential use in treating Chagas disease, a neglected parasitic disease in economically challenged tropical countries.