Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds of Dimorphandra gardneriana and Platymiscium floribundum, native plants from Caatinga biome

Abstract

In recent years, the Brazilian Health Ministry and the World Health Organization have supported research into new technologies that may contribute to the surveillance, new treatments, and control of visceral leishmaniasis within the country. In light of this, the aim of this study was to isolate compounds from plants of the Caatinga biome, and to investigate their toxicity against promastigote and amastigote forms of Leishmania infantum chagasi, the main responsible parasite for South American visceral leishmaniasis, and evaluate their ability to inhibit acetylcholinesterase enzyme (AChE). A screen assay using luciferase-expressing promastigote form and an in situ ELISA assay were used to measure the viability of promastigote and amastigote forms, respectively, after exposure to these substances. The MTT colorimetric assay was performed to determine the toxicity of these compounds in murine monocytic RAW 264.7 cell line. All compounds were tested in vitro for their anti-cholinesterase properties. A coumarin, scoparone, was isolated from Platymiscium floribundum stems, and the flavonoids rutin and quercetin were isolated from Dimorphandra gardneriana beans. These compounds were purified using silica gel column chromatography, eluted with organic solvents in mixtures of increasing polarity, and identified by spectral analysis. In the leishmanicidal assays, the compounds showed dose-dependent efficacy against the extracellular promastigote forms, with an EC50 for scoporone of 21.4µg/mL, quercetin and rutin 26 and 30.3µg/mL, respectively. The flavonoids presented comparable results to the positive control drug, amphotericin B, against the amastigote forms with EC50 for quercetin and rutin of 10.6 and 43.3µg/mL, respectively. All compounds inhibited AChE with inhibition zones varying from 0.8 to 0.6, indicating a possible mechanism of action for leishmacicidal activity.

Differential inhibition of human erythrocyte acetylcholinesterase by polyphenols epigallocatechin‐3‐gallate and resveratrol. Relevance of the membrane‐bound form

“…Interestingly, Ebrahimi and Schluesener described phenolic compounds as reversible inhibitors of AChE . Moreover, Vila‐Nova et al reported that some polyphenols were AChE inhibitors and at the same time leishmanicidal agents . Since erythrocyte‐associated AChE was studied in detail in our lab for many years, it was decided to analyze the possible inhibition of this isoform by phenolic compounds.…”

Phytochemicals in leaves of Cotoneaster mongolica, their antioxidative, and acetylcholinesterase inhibitory activity

“…Quercetin was also well studied for its AChE inhibitory activity. Researchers of different groups suggested that quercetin exhibited remarkable inhibitory activity with the IC 50 , 19.8 µM [33], the inhibitory activity 76.2 % [34] and the inhibition zone 0.6 cm [35], respectively. Compound 3 demonstrated a low activity for both DPPH scavenging and AChE enzyme inhibition.…”

Preparation and evaluation of the pentavalent antimony-quercetin complex (SbV-QUE)

“…Therefore, it is legitimate the search for more natural medications, with less toxicity and more efficiency. The quercetin is a flavonoid with recognized leishmanicidal activity against the amastigote stage of the Leishmania (Leishmania) donovani parasite (TASDEMIR et al, 2006;VILA-NOVA et al, 2012), L. (L.) amazonensis (MUZITANO et al, 2006) and for the amastigote and promastigote forms of L. (L.) infantum chagasi, with better results than secondline drugs such as amphotericin B and pentamidine (VILA-NOVA et al, 2012). Due to its electron-donor groups, the quercetin has chelating properties that allows it to complex with antimony.…”