Carla I. Nieto

A series of fourteen new asymmetrical 1,3-diketone derivatives have been synthesized and evaluated in the ABTS, FRAP and DPPH assays as a new chemotype with antioxidant and drug-like properties. All the compounds displayed low cytotoxicity in comparison to curcumin against the human neuroblastoma SH-SY5Y cell line. Among them, (3Z,5E)-6-(2,5-difluoro-4-hydroxy-phenyl)-1,1,1-trifluoro-4-hydroxyhexa-3,5-dien-2-one (6b) and (3Z,5E)-6-(2,3-difluoro-4-hydroxy-phenyl)-1,1,1-trifluoro-4-hydroxyhexa-3,5-dien-2-one (7b) with excellent solubility and chemical stability in biorelevant media, have also shown a similar Fe⁺² chelation behavior to that of curcumin. Additionally, both derivatives 6b and 7b have afforded good neuroprotection activity against H₂O₂ induced oxidative stress in the same neuronal cell line, with a significant reduction of intracellular ROS levels, in parallel with a good recovery of the Mitochondrial Membrane Potential (ΔΨ_m). Compounds 6b and 7b with a promising antioxidant and drug-like profile, with low cytotoxic and good neuroprotectant activity, constitute a new interesting chemical class with high potential as new therapeutic agents against neurodegenerative diseases.

The reaction of 1,2‐ethylenediamine with seven fluorinated β‐diketones affords two different 1,4‐diazepine series depending on the experimental conditions. Their structures as well as tautomerism have been established by ¹ H, ¹³ C, ¹⁵ N and ¹⁹ F nuclear magnetic resonance in solution supported by density functional theory calculations at the B3LYP/6‐311++G(d,p) level. The two compounds obtained from ( E )‐5‐(2‐fluoro‐4‐hydroxyphenyl)‐1‐phenylpent‐4‐ene‐1,3‐dione were analyzed by X‐ray crystallography and studied by solid‐state NMR.

The title compound, C₁₁H₁₂N₂, is not planar due to the folding of the seven-membered ring. In the crystal, molecules are packed opposite each other to minimize the electronic repulsion but the long intermolecular distances indicate that no directional contacts are found.

A group of 13 curcuminoid pyrazoles was investigated for their cytotoxicity on three tumoral cell lines (HT‐29, MCF‐7, and HeLa) and one non‐tumoral human cell line (HEK‐293). The values obtained were compared with those of curcumin. A subset of selected derivatives was also studied for their ability to downregulate expression of the hTERT and c‐Myc genes, which are both involved in telomerase activity.

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.

This paper reports the ¹H, ¹³C and ¹⁵N NMR experimental study of five benzimidazoles in solution and in the solid state (¹³C and ¹⁵N CPMAS NMR) as well as the theoretically calculated (GIAO/DFT) chemical shifts. We have assigned unambiguously the "tautomeric positions" (C3a/C7a, C4/C7 and C5/C6) of NH-benzimidazoles that, in some solvents and in the solid state, appear different (blocked tautomerism). In the case of 1H-benzimidazole itself we have measured the prototropic rate in HMPA-d₁₈.