Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Carla I NietoDarío Acuña-Castroviejo

Abstract

A series of new (E)-3(5)-[β-(aryl)-ethenyl]-5(3)-phenyl-1H-pyrazoles bearing fluorine atoms at different positions of the aryl group have been synthesized starting from the corresponding β-diketones. All compounds have been characterized by elemental analysis, DSC as well as NMR (¹H, (13)C, (19)F and (15)N) spectroscopy in solution and in solid state. Three structures have been solved by X-ray diffraction analysis, confirming the tautomeric forms detected by solid state NMR. The in vitro study of their inhibitory potency and selectivity on the activity of nNOS and eNOS (calcium-calmodulin dependent) as well as iNOS (calcium-calmodulin independent) isoenzymes is presented. A qualitative structure-activity analysis allowed the establishment of a correlation between the presence/ absence of different substituents with the inhibition data proving that fluorine groups enhance the biological activity. (E)-3(5)-[β-(3-Fluoro-4-hydroxyphenyl)-ethenyl]-5(3)-phenyl-1H-pyrazole (13), is the best inhibitor of iNOS, being also more selective towards the other two isoforms.

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Citations

Nov 22, 2018·Chemistry & Biodiversity·Satyendra MishraChandni G Halpani
Jun 9, 2016·Archiv der Pharmazie·Rosa Martí-CentellesRosa M Claramunt
May 11, 2017·Molecular Medicine Reports·Shaocheng ChenRui Wang
Aug 22, 2018·Medicinal Chemistry·Dolores Santa MaríaCelia Martín-Beltrán
Aug 20, 2020·Current Pharmaceutical Design·Marta Marín-LunaIbon Alkorta

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Methods Mentioned

BETA
NMR
X-ray
column chromatography

Software Mentioned

Bruker NMR
ORTEP ( Thermal Ellipsoid Plot
SHELXL

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