Ivermectin and curcumin cause plasma membrane rigidity in Leishmania amazonensis due to oxidative stress.

Spin label electron paramagnetic resonance (EPR) spectroscopy was used to study the mechanisms of action of ivermectin and curcumin against Leishmania (L.) amazonensis promastigotes. EPR spectra showed that treatment of the parasites with both compounds results in plasma membrane rigidity due to oxidative processes. With the IC 50 and EPR measurements for assays using different parasite concentrations, estimations could be made for the membrane-water partition coefficient (K M/W), and the concentration of the compound in the membrane (c m50) and in the aqueous phase (c w50), which inhibits cell growth by 50%. The K M/W values indicated that ivermectin has a greater affinity than curcumin for the parasite membrane. Therefore, the activity of ivermectin was higher for experiments with low cell concentrations, but for concentrations greater than 1.5 × 108 parasites/mL the compounds did not show significantly different results. The c m50 values indicated that the concentration of compound in the membrane leading to growth inhibition or membrane alteration is approximately 1 M for both ivermectin and curcumin. This high membrane concentration suggests that many ivermectin molecules per chlorine channel are needed to cause an increase in chlorine ion influx. [Display omitted] • Ivermectin and curcumin cause plasma membrane rigidity in Leishmania amazonensis. • Membrane rigidity results from an intense oxidative process of membrane proteins. • The affinity for the parasite membrane is greater for ivermectin than for curcumin. • To exert their activities, molecules accumulate in the membrane in large amounts. [ABSTRACT FROM AUTHOR]