TY - JOUR
T1 - Design, Synthesis and Docking Calculations of Prenylated Chalcones as Selective Monoamine Oxidase B Inhibitors with Antioxidant Activity
AU - Mellado, Marco
AU - Salas, Cristian O.
AU - Uriarte, Eugenio
AU - Viña, Dolores
AU - Jara-Gutiérrez, Carlos
AU - Matos, Maria J.
AU - Cuellar, Mauricio
N1 - Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/7/12
Y1 - 2019/7/12
N2 - Different natural and synthetic chalcones have exhibited selective inhibition on monoamine oxidase B (MAO−B) activity, demonstrating potential interest for the treatment of neurodegenerative diseases. Herein we report the synthesis of seven new prenylated chalcones (7a-g) obtained from the natural compound 5 (4-hydroxy-3-(3-methylbut-2-en-1-yl)phenylethanone), previously isolated from S. graveolens. Five of these compounds exhibit high inhibition and selectivity against MAO−B, with IC50 values in the low micromolar range. In addition, the antioxidant activity of this series was measured, being three compounds better than the reference, butylated hydroxytoluene (BHT). Compound 7 f [(2E)-3-(4-(dimethylamino)phenyl)-1-(4-hydroxy-3-(3-methylbut-2-en-1-yl)phenyl)prop-2-en-1-one] proved to be the best compound within the studied series (IC50 MAO-B=8.19 μM and k DPPH=3.73). Finally, molecular docking was performed to better understand the binding properties of these derivatives. Important features for MAO−B inhibitory activity were observed: hydrogen-bonding interaction between Tyr435 and nearness with Tyr398 and FAD co-factor. Therefore, these molecules are good candidates for the design of a lead compound for Parkinson's disease.
AB - Different natural and synthetic chalcones have exhibited selective inhibition on monoamine oxidase B (MAO−B) activity, demonstrating potential interest for the treatment of neurodegenerative diseases. Herein we report the synthesis of seven new prenylated chalcones (7a-g) obtained from the natural compound 5 (4-hydroxy-3-(3-methylbut-2-en-1-yl)phenylethanone), previously isolated from S. graveolens. Five of these compounds exhibit high inhibition and selectivity against MAO−B, with IC50 values in the low micromolar range. In addition, the antioxidant activity of this series was measured, being three compounds better than the reference, butylated hydroxytoluene (BHT). Compound 7 f [(2E)-3-(4-(dimethylamino)phenyl)-1-(4-hydroxy-3-(3-methylbut-2-en-1-yl)phenyl)prop-2-en-1-one] proved to be the best compound within the studied series (IC50 MAO-B=8.19 μM and k DPPH=3.73). Finally, molecular docking was performed to better understand the binding properties of these derivatives. Important features for MAO−B inhibitory activity were observed: hydrogen-bonding interaction between Tyr435 and nearness with Tyr398 and FAD co-factor. Therefore, these molecules are good candidates for the design of a lead compound for Parkinson's disease.
KW - Antioxidant activity
KW - Claisen-Schmidt reaction
KW - Molecular docking
KW - Monoamine oxidase B inhibitors
KW - Prenyl-chalcones
UR - http://www.scopus.com/inward/record.url?scp=85068955355&partnerID=8YFLogxK
U2 - 10.1002/slct.201901282
DO - 10.1002/slct.201901282
M3 - Article
AN - SCOPUS:85068955355
VL - 4
SP - 7698
EP - 7703
JO - ChemistrySelect
JF - ChemistrySelect
SN - 2365-6549
IS - 26
ER -