Synthesis, structure and biological activity of 3(5)-trifluoromethyl-1H-pyrazoles derived from hemicurcuminoids

Effects of Curcuminoid Pyrazoles on Cancer Cells and on the Expression of Telomerase Related Genes

“…We carried out a measurement of the cytotoxic activity of our synthetic curcuminoid pyrazoles on three tumoral cell lines: the human colon HT‐29, the breast adenocarcinoma MCF‐7, and the cervix adenocarcinoma HeLa, as well as one non‐tumoral cell line: the human embryonic kidney cell line HEK‐293 . Table shows the cytotoxicity values for curcuminoids 1 and 10 – 21 , expressed as the compound concentration (μM) that causes 50% inhibition of cell growth (IC 50 ).…”

“…Compounds 1 , 10 – 21 were prepared by reaction of the corresponding β‐diketones with hydrazine hydrate 98% (Scheme ), as already described by us in Refs. .…”

“…Correlation of the present results with those concerning our studies on the inhibitory activities of the same compounds against the three NOS isoforms is not obvious. As a whole, our pyrazoles exhibited a major inhibition of the inducible iNOS isoform versus the constitutive isoforms nNOS and eNOS, those with fluorine atoms at positions 2' and 3' showing the higher inhibition percentages . A statistical analysis of the inhibition percentages together with the selectivity coefficients α , β , and γ (from this paper) for curcuminoids 1 and 10 – 21 , using a Free‐Wilson matrix differentiating the fluorine atoms according to their position [7b], has shown that the six properties are independent.…”

“…Curcumin is commercially available and was used after purification by crystallization from ethanol/water. ( E )‐3,5‐Bis[β‐(4‐hydroxy‐3‐methoxyphenyl)‐ethenyl]‐1 H ‐pyrazole ( 1 ), ( E )‐3‐[β‐(2‐fluoro‐4‐hydroxyphenyl)‐ethenyl]‐5‐trifluoromethyl‐1 H ‐pyrazole ( 10 ), ( E )‐3‐[β‐(3‐fluoro‐4‐hydroxyphenyl)‐ethenyl]‐5‐trifluoromethyl‐1 H ‐pyrazole ( 11 ), ( E )‐3‐[β‐(2,4‐difluoro‐3‐hydroxyphenyl)‐ethenyl]‐5‐trifluoromethyl‐1 H ‐pyrazole ( 12 ), ( E )‐3‐[β‐(2,5‐difluoro‐4‐hydroxyphenyl)‐ethenyl]‐5‐trifluoromethyl‐1 H ‐pyrazole ( 13 ), ( E )‐3‐[β‐(4‐fluoro‐3‐methoxyphenyl)‐ethenyl]‐5‐trifluoromethyl‐1 H ‐pyrazole ( 14 ), ( E )‐3‐[β‐(4‐hydroxy‐3‐methoxyphenyl)‐ethenyl]‐5‐trifluoromethyl‐1 H ‐pyrazole ( 15 ), ( E )‐3‐[β‐(2‐fluoro‐4‐hydroxyphenyl)‐ethenyl]‐5‐phenyl‐1 H ‐pyrazole ( 16 ), ( E )‐3‐[β‐(3‐fluoro‐4‐hydroxyphenyl)‐ethenyl]‐5‐phenyl‐1 H ‐pyrazole ( 17 ), ( E )‐3‐[β‐(2,4‐difluoro‐3‐hydroxyphenyl)‐ethenyl]‐5‐phenyl‐1 H ‐pyrazole ( 18 ), ( E )‐3‐[β‐(2,5‐difluoro‐4‐hydroxyphenyl)‐ethenyl]‐5‐phenyl‐1 H ‐pyrazole ( 19 ), ( E )‐3‐[β‐(4‐fluoro‐3‐methoxyphenyl)‐ethenyl]‐5‐phenyl‐1 H ‐pyrazole ( 20 ), and ( E )‐3‐[β‐(4‐hydroxy‐3‐methoxyphenyl)‐ethenyl]‐5‐phenyl‐1 H ‐pyrazole ( 21 ) were crystallized from the appropriate solvent and their purity checked by thin layer chromatography and analytical techniques.…”

“…Our past contribution to this field has consisted in four publications devoted to pyrazoles 1 and 10 – 21 (Fig. ) as new therapeutic agents in inflammatory bowel disease , their annular tautomerism , and NOS inhibition . We have also been active in the field of curcumin and the curcuminoids .…”