Scientists
seek to design therapeutically more potent chemicals from alkaloids produced by
the plant, Uncaria guianensis, which
could aid in combatting tumours.
Researchers
have prepared modified forms of the alkaloids produced by Uncaria guianensis (also known as cat’s claw), a plant native to
the Amazon Rainforest, whose natural versions of alkaloids are widely used to
combat tumours and inflammation and can help modulate the immune system.
The
scientists from Brazil sought to design therapeutically more potent chemicals
from these alkaloids.
Recent
studies have shown that modifications in the chemical structure of certain
alkaloids can enhance their therapeutic effects. Fluorovinblastine, for
example, results from the addition of fluorine to the chemical structure of
vinblastine, a natural alkaloid produced by the Rosy periwinkle (Catharanthus roseus).
When
we compared the structure of vinblastine and of the alkaloids from U. guianensis, we found highly similar
biosynthetic pathways,†said Adriana Aparecida Lopes, a professor at the
University of Ribeirão Preto and first author of the article. “One of the
modifications we made was therefore similar: we substituted a fluorine atom for
a hydrogen in the aromatic ring [a small part of the structure of the
molecule].â€
The
outcome of this small modification was a new alkaloid called
6-fluoro-isomitraphylline, which has three aromatic hydrogens and one fluorine
instead of the natural alkaloid’s four aromatic hydrogens. The researchers also
produced an analogue called 7-methyl-isomitraphylline by substituting a methyl
group for an aromatic hydrogen.
In the
study, modifications were made to the alkaloids using U. guianensis‘s own metabolic pathways. Plantlets (young plants)
were grown in the laboratory and were fed with water and nutrients. Precursors
of the natural alkaloids with small modifications to their structures were
added to this liquid medium.
“This
protocol is called precursor-directed biosynthesis,†Lopes explained. “The
synthesis is done by the plant. I provide it with an analogous key intermediate
[precursor], which is captured and inserted into its metabolic route, forming a
new alkaloid.â€
The
plants were grown for 30 days and then extracted. The extracts were subjected
to different types of liquid chromatography and mass spectrometry to identify
the substances present in the extract based on their corresponding ions.
Following this, chemical processes were used to isolate the alkaloid analogues.
Using
this method, approximately one to two milligrams of the new alkaloids were
obtained. The next steps will entail increasing the output.
The team expects the therapeutic efficacy of the novel compounds obtained from U. guianensis using precursor-directed biosynthesis to be more potent than those produced naturally by the plant.
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