O-geranylchalcones: synthesis and metabolic inhibition against Leishmania mexicana and Trypanosoma cruzi

In this paper, twelve substituted O-geranylchalcones were synthesized and evaluated for their leishmanicidal and trypanocidal activity. All the synthesized compounds showed selective activity against L. mexicana strain in comparison to T. cruzi strain. O-geranyl chalcone 5j substituted with a meta-NO2 group in B ring, showed the highest selectivity (IS = 21.46). Cytotoxicity studies using murine macrophages J774.A1 showed that F and Cl substituents on the para position on the B ring, displayed the less toxicity as in compounds 5f and 5i. Calculated ADME properties indicated that the obtained chalcones presented a good skin permeability, making them adequate candidates for local treatment of cutaneous leishmaniasis.