Eugenol carbonate activity against Plasmodium falciparum , Leishmania braziliensis , and Trypanosoma cruzi

CLEMENTE, CAMILA M.; PINEDA, TATIANA; UPEGUI, YULIETH; YEPES, LINA M.; ALLEMANDI, DANIEL A.; ROBLEDO, SARA M.; RAVETTI, SOLEDAD

ARCHIV DER PHARMAZIE.

WILEY-V C H VERLAG GMBH

Año: 2021 p. 1 - 11

0365-6233

Neglected tropical diseases are a major health problem throughout the world, and thereare few effective and safe drugs. In this study, we report the design and synthesis of anovel series of carbonates of eugenol using different aliphatic alcohols and N,N‐carbonyldiimidazole. Spectroscopic techniques, including 1H nuclear magnetic resonance(NMR), 13C NMR, Fourier transform infrared, and high‐resolution mass spectrometry,were used to confirm the structures of the synthesized compounds. In vitro and in silicostudies of prodrugs of eugenol were performed to determine their antiplasmodial, trypanocidal, and leishmanicidal activities, and also their cytotoxicity. Compounds werehighly active against Leishmania braziliensis and Plasmodium falciparum, whereas the activity shown for Trypanosoma cruzi was moderate. Molecular docking was used to determine a possible mode of action of eugenol against the dihydroorotate dehydrogenaseof the three parasites (TcDHODH, LbDHODH, and PfDHODH). Notably, the dockingresults showed that eugenol not only has binding energy similar to that of the naturalsubstrate (−7.2 and −7.1, respectively) but also has interactions with relevant biologicalresidues of PfDHODH. This result indicates that eugenol could act as a substrate forPfDHODH in the pyrimidine biosynthesis pathway of P. falciparum. In conclusion, thecombination of certain aliphatic alcohols and eugenol through a carbonate bond couldsignificantly increase the antiparasitic activity of this class of compounds, which meritsfurther studies.