Summary:
In the context of the present MSc dissertation a series of hydrazones of
5-nitro-2-furaldehyde with adamantanalkanohydrazides were designed, synthesized
and had their activity against African and American Trypanosomiasis evaluated.
From the synthetic point of view, the course of reactions comprises the
following steps:
1. Preparation of 1- or 2-adamantanalkanoic ethyl esters.
2. Preparation of adamantanalkanohydrazides, by reacting hydrazine
hydrate with the aforementioned esters, mostly in diethylene glycol using a
microwave apparatus.
3. Synthesis of the final products, by reacting carbohydrazides with
either 2-furaldehyde or 5-nitro-2-furaldehyde in ethanol.
The study of the 1H and 13C-NMR spectra revealed that most of the
carbohydrazones are mixtures of conformers, the structures of which were
elucidated using molecular mechanics and quantum mechanical methods.
The trypanocidal activity assay proved that carbohydrazones, which have a
nitro-group, are active at nM scales against both T. cruzi and T. brucei.
Conversely, derivatives not bearing a nitro-group on the furan ring are
practically inactive against both parasite types. In addition, C1-substitued
adamantane derivatives appear to be more selective active against T. cruzi,
while C2-substitued adamantane derivatives appear to be more selective against
T. brucei. Lastly, the introduction of a hydrophobic substituent on C3 appears
to enhance the trypanocidal activity.
Keywords:
Hydrazones of 5-nitro-2-furaldehyde, Adamantanalkanohydrazides, Trypanocidal activity, Trypanosoma cruzi, Trypanosoma brucei
