COMPARATIVE STUDY OF DEHYDRODIEUGENOL AND ITS METHYLATED DERIVATIVES IN LANGMUIR MONOLAYERS

Dehydrodieugenol and its mono and permethylated derivatives, prepared by its methoxylation, are known to display antiparasitic activities¹. The monomethylated derivative was tested in vivo against extracellular and intracellular forms of T. cruzi, showing an expressive selectivity toward amastigotes forms of the parasite and NCTC cells (IC50=8.2 μM and SI>24) and an enhancement of the antiparasitic potential observed to dehydrodieugenol (IC50=15.1 μM) and the permethylated derivative. Aiming to understand these results better, interactions between the drugs and components of protozoa cell membranes were studied by Langmuir monolayers. The parasite membrane was represented by phosphatidylcholine (DPPC), phosphatidylethanolamine (DPPE), phosphatidylserine (DPPS), and phosphatidylglycerol (DPPG) monolayers. Tensiometric, spectroscopic and morphologic measurements were performed. While dehydrodieugenol interacted more with the hydrophilic portion of the lipids, highlighting some similarities between the negatively charged lipids, the monomethylated derivative altered the carbonyl chains order of the lipids. DPPE and DPPG were similarly affected by monomethylated derivative, which could be related to their protonated amine group. On the other hand, the permethylated derivative caused similar effects to all lipid isotherms but more expressively in DPPG. The interactions showed that the lipid composition and drug hydrophobicity tune drug-lipid interaction. We expect to correlate these results with the drug’s antitrypanosomal action. Acnowledgements: CAPES, FAPESP, CNPq.

1. Grecco S.S. et al., Antitrypanosomal activity and evaluation of the mechanism of action of dehydrodieugenol isolated from Nectandra leucantha (Lauraceae) and its methylated derivative against Trypanosoma cruzi. Phytomedicine 2017, 24, 62-67.