Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin Nieto, Carla I. Cabildo, María Pilar Cornago, María Pilar Sanz, Dionisia Claramount, Rosa M. Torralba, María del Carmen Torres, María Rosario Elguero, José García, José A. López Ramírez, Ana Acuña Castroviejo, Darío NOS inhibitors Pyrazoles Tautomerism Fluorine derivatives Curcumin Crystallography Multinuclear NMR 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, 13C, 19F and 15N) 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. 2015-11-11T10:58:46Z 2015-11-11T10:58:46Z 2015 info:eu-repo/semantics/article Nieto, C.I.; et al. Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin. Molecules, 20(9): 15643-15665 (2015). [] 1420-3049 http://hdl.handle.net/10481/38791 10.3390/molecules200915643 eng http://creativecommons.org/licenses/by-nc-nd/3.0/ info:eu-repo/semantics/openAccess Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License MDPI