Singly and doubly modified analogues of C20-epi-salinomycin: A new group of antiparasitic agents against Trypanosoma brucei

Abstract Polyether ionophores, with >120 molecules belonging to this group, represent a class of naturally-occurring compounds that exhibit broad range pharmacological properties, including promising activity towards variety parasites. In context, salinomycin (SAL) seems be interesting, as ionophore has been found active against parasites are responsible for number human and animal diseases. On the other hand, less explored is investigation into anti-parasitic SAL derivatives. Recently, we identified C1 amides esters its analogue, C20-oxosalinomycin, structures trypanocidal drug candidates. search novel effective African trypanosomes, synthetic access completely new series C20-epi-salinomycin (compound 2) analogues described in paper. This includes products obtained via derivatisation either carboxyl or C20 hydroxyl 2, but also C1/C20 double modified The anti-trypanosomal well cytotoxic these were evaluated bloodstream forms T. brucei myeloid HL-60 cells, respectively. It was single derivatives 8, 12, 18 (C20 decanoate, ethyl carbonate, allophanate respectively) most selectively targeting bloodstream-form 50% growth inhibition (GI50) values 0.027–0.043 ?M selectivity indices 165–353. These results indicate modification at position 2 can provide semi-synthetic enhanced could great value development drugs treat trypanosomiasis.