Antiparasitic Derivatives of the Furoquinoline Alkaloids Kokusaginine And Flindersiamine

FERNÁNDEZ, LUCÍA RAQUEL; SÁENZ, DANIEL; AVIGLIANO, ESTEBAN; BERNAL GIMÉNEZ, DIANA MARÍA; FERRI, GABRIEL; CASAS, ADRIANA; PALERMO, JORGE ALEJANDRO; BELÉN VALDEZ, MARÍA; MUSIKANT, ALEJANDRO DANIEL; DI VENOSA, GABRIELA; EDREIRA, MARTÍN MIGUEL

CHEMMEDCHEM

WILEY-V C H VERLAG GMBH

Año: 2022 vol. 17

1860-7179

We report the synthesis of 16 new compounds obtained from kokusaginine and flindersiamine, the main alkaloids isolated from the bark of Balfourodendron riedelianum. The activity of the compounds against axenic cultures of Trypanosoma cruzi epimastigtotes and trypomastigotes, as well as intracellular amastigotes, is described, together with their cytotoxic activity against three different human cell lines. The synthetic strategy for the preparation of the new compounds was based on the reactivity at the C4 position of the furoquinoline core towards nucleophiles. The new derivatives were synthesized by a Buchwald-Hartwig reaction, in most cases under green, solventfree conditions. Compounds 1c and 1e displayed better in-vitro activity against trypomastigotes than benznidazole and nifurtimox (positive controls) with IC50