Biological Evaluation of 3-Benzylidenechromanones and Their Spiropyrazolines-Based Analogues

Abstract

A series of 3-benzylidenechrmanones 1, 3, 5, 7, 9 and their spiropyrazoline analogues 2, 4, 6, 8, 10 were synthesized. X-ray analysis confirms that compounds 2 and 8 crystallize in a monoclinic system in P21/n space groups with one and three molecules in each asymmetric unit. The crystal lattice of the analyzed compounds is enhanced by hydrogen bonds. The primary aim of the study was to evaluate the anti-proliferative potential of 3-benzylidenechromanones and their spiropyrazoline analogues towards four cancer cell lines. Our results indicate that parent compounds 1 and 9 with a phenyl ring at C2 have lower cytotoxic activity against cancer cell lines than their spiropyrazolines analogues. Analysis of IC50 values showed that the compounds 3 and 7 exhibited higher cytotoxic activity against cancer cells, being more active than the reference compound (4-chromanone or quercetin). The results of this study indicate that the incorporation of a pyrazoline ring into the 3-arylideneflavanone results in an improvement of the compounds’ activity and therefore it may be of use in the search of new anticancer agents. Further analysis allowed us to demonstrate the compounds to have a strong inhibitory effect on the cell cycle. For instance, compounds 2, 10 induced 60% of HL-60 cells to be arrested in G2/M phase. Using a DNA-cleavage protection assay we also demonstrated that tested compounds interact with DNA. All compounds at the concentrations corresponding to cytotoxic properties are not toxic towards red blood cells, and do not contribute to hemolysis of RBCs.

Regioselective Access to 3‐Ethylideneflavanones via Rhodium(I)‐Catalyzed 1,3‐Enyne Hydroacylation/Annulation Cascades

“…In view of the fact that the resulting 3‐alkylideneflavanones have gathered considerable momentum in the field of medicinal chemistry (Figure 1), [10] this appealing but challenging regiocontrolled strategy would offer a valuable synthetic transformation. Furthermore, in contrast with the conventional methods for the synthesis of 3‐alkylideneflavanones from 2‐hydroxyacetophenones and aromatic aldehydes involving tedious procedures, [10b,c,d] this one‐pot protocol achieved 100% atom‐economy efficiency and displayed excellent functional group tolerance and remarkable regioselectivity under mild reaction conditions.…”

Pyrazoline Hybrids as Promising Anticancer Agents: An Up-to-Date Overview

“…Sim et al reported [ 26 ] the use of purinimide-pyrazoline compounds (e.g., derivative 1 ) ( Figure 4 ) and their polyoxometalate complexes as photosensitizers in photodynamic therapy. Recently, Budziz and co-workers documented the biological evaluation of a series of chromanone-spiro-1-pyrazoline hybrids [ 27 ]. Among them, 2 was found to be the most cytotoxic against HL-60, NALM-6, and WM-115 cell lines (IC 50 = 3.0–6.8 μM).…”

Recent Advances in Photo‐mediated Radiofluorination

“…A wide scope of substrates was 18 F‐radiofluorinated within this transformation to generate corresponding 18 F‐labeled products 35 at a moderate RCY. Particularly, 18 F‐labelled compound 35 a was synthesized in 20% RCY (after isolation) from 4‐chromanone, which is a vital scaffold in many anticancer candidates [39] . It is noteworthy that this product (compound 35 a ) was not prepared in their previously reported method and only by‐products were obtained after the reaction was finished.…”