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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
&
In silico
and
in vivo
assays of a borinic DOPA-derivative for Parkinson disease
Marvin A Soriano-Ursúa, Ana L Ocampo-Néstor, Antonio Abad-García
and
José G Trujillo-Ferrara
Instituto Politécnico Nacional, Mexico
T
he boron atomhas some chemical propertieswhich confer it
advantages to be added in potential newdrugs. One of these
advantages has been inferred by
in silico
assays interaction on
receptors or proteins with serine, threonine or tyrosine on the
active site. In this sense, catecholamine receptors (belonging
to the G-protein coupled receptors family) have a conserved
binding site with three serine-residues involved in receptor
activation. In this work, we tested the potential activity of 3-D
models representing adducts of levodopa or dopamine on
models of catecholamine human receptors (emphasis on beta-
adrenoceptors and D2 and D3 receptors) by
in silico
docking
analyses. Then, we synthesized and characterized a compound
with potential activity on D2 receptor judged with the affinity
score and binding mode on this receptor. Interestingly, the
boron-containing compound contacts on the orthosteric site
with higher affinity than Levodopa or dopamine, but its boron
atom is not directed to serine residues in fifth transmembrane
domain. This compound is an adduct of levodopa and an aryl-
diphenylborinic acid, which was tested in a C57/BL6-mice
model of parkinsonism induced by peritoneal administration of
MPTP (a well-known toxin on catecholaminergic system). The
compound induced improved performance of administered
mice on motor tests but several pharmacological tests are
required to elucidate the putative mechanism of action.
Speaker Biography
Marvin A Soriano-Ursúa has completed his PhD from Escuela Superior de Medicina
del Instituto Politénico Nacional, México. He is a Member of the National System
of Researchers, and he is Head of the Physiology Laboratory. He has focused on the
rational drug design having boron-containing compounds as main moiety, as well
as, the different effects of these compounds on human physiology, particularly on
G-Protein coupled receptors. He has authored more than 35 publications that have
been cited over 200 times, and he has been serving as an Editorial Board Member and
Reviewer of repute scientific journals.
e:
soum13mx@gmail.com