Iboga alkaloids are
a group of monoterpenoid indole alkaloids with
promising and intriguing biological activities. Ibogaine is the representative
member of the series and has become widely known as a potent atypical
psychedelic with promising effects to treat substance use disorder.
Nowadays, an efficient and scalable enantioselective total synthesis
of ibogaine and related iboga alkaloids is still lacking, so direct
extraction from natural sources or semi-synthetic schemes are the
methods of choice to obtain them in a preparative scale. In particular,
ibogaine can be obtained either by a low yielding direct isolation
from Tabernanthe iboga or using a semi-synthetic
procedure from voacangine, an iboga alkaloid occurring in a higher
yield in the root bark of Voacanga africana. In this work, we describe an optimized process to obtain voacangine
from V. africana root bark as a precursor
of the iboga scaffold. Using a direct acetone-based extraction procedure
(0.5 kg of root bark), voacangine was isolated in ∼0.8% of
root bark dried weight, while the major alkaloids isolated from the
bark were identified as iboga-vobasinyl dimers (∼3.7%) such
as voacamine and voacamidine. Since these alkaloids contain the voacangine
moiety in their structure, the cleavage of the dimers was further
optimized, affording an extra amount of voacangine in ∼50%
isolated molar yield. In this manner, the total amount of voacangine
obtained by application of the whole procedure to the plant material
(extraction and dimer cleavage) could almost duplicate the content
originally found in the root bark.
Introduction: Chagas disease and Leishmaniasis are among the most important parasitic diseases. They are considered to be within the most relevant group of neglected tropical diseases and have been included as priorities for searching new drugs due to their several treatment limitations. These parasitic diseases caused by flagellated protozoans affect more than 20 million people predominantly in developing countries.
Methodology: In this study, we prepared a series of 2-substituted 1,4-benzenediols by an efficient, green, and lithium salt-free synthesis in water/ethanol as solvent to test their anti-parasitic activity. All 36 phenolic derivatives were evaluated in vitro for their activity against T. cruzi epimastigotes, L. infantum, and L. braziliensis promastigotes, as well as their cytotoxicity on macrophage and fibroblast cell lines.
Results: Based on the results obtained, the compounds that presented a methyl, trifluoromethyl or bromo group at the para-position of the second benzene ring were found the most active analogs, with higher selective index values on the three parasites assayed.
Conclusion: This evidence suggests that the anti-parasitic activity observed in these analogs is affected by the size of the group at the 4-position of the second ring, but not related with electronic factors.This study identified hit compounds with the potential to target several kinetoplastid parasites.
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