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J Pharmacol Ther Res 2017 Volume 1 Issue 2
November 02-03, 2017 Chicago, USA
4
th
International Congress on
International Conference and Exhibition on
Drug Discovery, Designing and Development
Biochemistry, Molecular Biology: R&D
&
Natural isoquinoline alkaloids as potential multi-target agents against Alzheimer’s disease
Erika Plazas G, Avila M C, Sandoval A
and
Cuca L E
Universidad Nacional de Colombia, Colombia
Statement of the Problem:
Alzheimer’s disease (AD) is the
most prevalent neurodegenerative disorder and main form
of dementia in elder people. AD is a multifactorial disorder
with a complex pathogenesis, characterized by a progressive
loss of memory and other cognitive abilities, associated
with cholinergic detriment. Currently, cholinesterase
inhibitors are the only approved drugs for treatment of
AD; however, these only improve cognitive ability and have
significant side effects. Consequently, the development
for new therapeutically agents more effective and safety
is necessary. Multi-target therapy is an innovative strategy
focused on the treatment of complex diseases which arises
to overcome lack of traditional paradigm “one molecule-one
target”. New generation of multi-target agents required not
only to improve symptoms, but also to modify the disease.
Methodology:
We achieved the AChEI-targeted isolation
of isoquinoline alkaloids from
Ocotea discolor
(
Lauraceae
)
and
Zanthoxylum schreberi
(
Rutcaeea
). Based on the amyloid
hypothesis, was evaluated themultimodal potential. Thus, were
assessedtheanticholinergicactivityagainstacetylcholinesterase
(AchE) and butyrylchlolinesterase (BChE); antioxidant capacity
(DPPH and β- carotene) and LXR agonists activity.
Findings:
The studied species were selected from a previous
screening of antioxidant and anticholinergic activity carried
out in our laboratory. From the wood of
O. discolor
were
isolated 3 aporphine alkaloids ocoxilonine, ocoteine and
dicentrine. On the other hand, from the stem bark of
Z.
schreberi
were isolated 2 protoberberines (berberine and
columbamine) and a benzophenanthridine (chelerythrine).
Four of the isolated alkaloids showed strong inhibition
of AChE with IC50 lower than 50 µg/mL. Most of these
were more active against AChE than BChE, nevertheless,
columbamine and ocoxilonine were selective against BChE.
The aporphine alkaloids presented highest antioxidant
capacity. Additionally, the isolated alkaloids showed potential
inhibition of LXR.
Conclusion&Significance:
Isoquinoline alkaloids havemultimodal
prospective due to their activity against different AD targets,
abundant distribution and fewpharmacological studies.
Speaker Biography
Erika Plazas G is a PhD student, Chemist withMaster’s in Science degree. Her experience
in Natural Products Chemistry has been encouraging a growing interest in Medicinal
Chemistry and Bioprospecting. Also, she has experience in research, evaluation,
teaching and experimental work, specifically in Phytochemistry, Organic and Analytical
Chemistry. Additionally, she has skills in natural products, biological activity assays,
extraction, purification and identification techniques and management of instrumental
(HPLC and GC) and spectroscopic (UV, IR, MS and NMR) methods, as well as, programs
for multivariate statistical analysis (PCA, OPLS-DA) focused on metabolomic studies.
e:
eaplazasg@unal.edu.co