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CNS 2016
December 05-07, 2016
Volume 7, Issue 5(Suppl) J Neurol Neurophysiol
ISSN: 2155-9562 JNN, an open access journal
conferenceseries .com
December 05-07, 2016 Dubai, UAE
2nd International Conference on
Central Nervous System Disorders & Therapeutics
Slavikova Barbora et al., J Neurol Neurophysiol 2016, 7:5(Suppl)
Architecture in the synthesis of steroidal inhibitors of NMDA receptors: Do built new or rebuilt
old?
Slavikova Barbora, Kapras Vojtech, Ulli Jahn, Vyklicky Ladislav, Chodounska Hana and Kudova Eva
Academy of Sciences of the Czech Republic, Czech Republic
Ourmain avenue of investigation is design and synthesis of steroidal inhibitors of N-methyl-D-aspartate receptors (NMDAR)
that could serve as drug-like candidates for CNS disorders as these receptors are essential for synaptic plasticity, learning
and memory. However, under pathological conditions, the over-excitation of the NMDAR can induce cell death. Our ongoing
structure-activity relationship studies (SAR) are focused on structural modifications of steroidal skeleton that would afford
potent inhibitors of NMDAR. In general, the inhibitory effect of neurosteroids on NMDAR is dependent upon the 5β-pregnane
skeleton. To elucidate the SAR of the pregnane acetyl moiety, we have prepared a series of compounds with lipophilic D-ring
modifications and showed that these analogues are more potent modulators of NMDA-induced currents (IC50 values varying
from 90 nM to 5.4 μM) than the known endogenous neurosteroid- pregnanolone sulfate (IC50=24.6 μM). The obtained results
emerged us to assess the structural motif of the steroidal D-ring. As such, a series of compounds with partially of fully degraded
D-ring was synthesized (IC50 values varying from 15 μM to 224 μM). Finally, using the total synthesis of steroidal A, B and
C-ring, we have prepared a series of compounds with non-steroidal structural characteristics of various types that allowed us
to define new structural motifs for inhibitors of NMDA receptors.
Biography
Slavikova Barbora has received her Master’s degree in 1983 from the Institute of Chemical Technology in Prague. She has been working at the Institute of Organic
Chemistry and Biochemistry, Academy of Sciences of the Czech Republic in Prague for almost 25 years with specialization in steroidal synthesis. During this period,
she has synthesized thousands of compounds and is the author and co-author in 18 original papers and 4 patents.