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Clinical Pharmacology & Biopharmaceutics | ISSN : 2167-065X
Volume 7
September 18-19, 2018 | Amsterdam, Netherlands
6
th
European Biopharma Congress
Euro Biopharma 2018
Jana Tchekalarova et al., Clin Pharmacol Biopharm 2018, Volume:7
DOI: 10.4172/2167-065X-C1-029
Neuropharmacological studies of novel melatonin derivatives
T
he majority of available literature on experimental animals revealed that melatonin has
anticonvulsant action in acute seizures tests with different mechanism of action. An
important advantage of melatonin as an add-on option in a therapy of epilepsy is associated
withitslowtoxicity,antioxidantactivityaswellasitsabilitytosynchronizedisturbedcircadian
rhythms in epileptic patients. A series of melatonin analogues, containing indole scaffold,
were synthesized and their anticonvulsant activity was tested on ICR mice by measuring the
time of three different seizure phases (myoclonic, clonic and tonic) induced by intravenous
infusion of pentylenetetrazol (PTZ). The novel melatonin derivatives were synthesized
according to the classical method by condensation of hydrazones with 5-methoxyindole-
3-carboxaldehyde or 5-benzyloxyindole-3-carboxaldehyde. The hydrazide-hydrazones
with indole moyeties were purified by recrystallization and the molecular weights were
determined, using ES-MS. The compounds were injected intraperitoneally at doses of 30,
60 and 100 mg/kg 30 min before PTZ. The most potent compounds, with significantly
increased thresholds for myoclonic, clonic and tonic seizures compared to vehicle were
the derivatives with 2-thienyl and p-Cl-phenyl fragments at a dose of 60 mg/kg, which
effects was comparable to that of melatonin at the same dose of 60 mg/kg, used as a
positive control. None of the compounds displayed neurotoxicity in the rota-rod test.
In
silico
assessment of their BBB permeability indicated them as CNS active agents. Molecular
docking was performed into a human gamma-aminobutyric acid (GABA
A
) receptor and
depicted good binding properties of melatonin derivatives, considered in this study. Based
on anticonvulsant screening results, these newly synthesized melatonin derivatives will be
explored in other seizure tests with different mechanism of action as well as in models of
epilepsy.
Biography
Jana Tchekalarova has completed her PhD in Pharmacology in 2004 from Institute of Physiology, BAS. She has 22
years of research experience. She is currently working as an Associate Professor at the Institute of Neurobiology,
BAS and as the Head of Behavioral Neurobiology Dept. She is an Adjunct Professor at the Section of Biochem.,
Physiology and Pathophysiology in the Med. Dept. of Sofia University.According to Mendeley profile her h-index=12,
publications 51 with IF; citations=385. She has more than 500 citations. She has been serving as an Editorial Board
Member of
Drug Development Research, Journal of Neurological Disorders and Stroke
and Asian Council of Sci
Editors.
janetchekalarova@gmail.comJana Tchekalarova
Institute of Neurobiology
Bulgaria
Co-Authors
Violina T Angelova
2
, Tania
Pencheva
3
and Pavlina
Andreeva-Gateva
3
2
Medical University of Sofia, Bulgaria
3
Institute of Biophysics &
Biomedical Engineering- BAS, Bulgaria