Naringenin is one of the most abundant dietary flavonoids, predominantly found in citrus fruits and grapes. This compound exerts several pharmacological activities: its antioxidant, antiviral, anti-inflammatory, anti-carcinogenic and cardio-protective effects have been reported.[1-3] Due to its several beneficial biological activities, the design and synthesis of novel naringenin derivatives is of continuous interest.
During the current work our aim was to synthesize a compound library of oxime and oxime-ether derivatives of naringenin, and to test their in vitro antitumor activity on different cancer cell lines, as well as their antioxidant activity.
Seven compounds have been prepared. When using hydroxylamine as reagent, the formation of geometric isomers was observed, and the obtained E- and Z-oximes were separated by flash chromatography. On the other hand, stereospecific formation of the E-oxime ethers were observed with alkoxylamines. The structure of the prepared compounds was confirmed by NMR and HRMS measurements.
Antiproliferative activity of the prepared compounds was evaluated by MTT assay against human leukemia cells and a gynecological cancer cell line panel. Compound 6 exerted the most potent activity with IC50 values of 19.5, 23.5, 29.7, 31.8 and 35.4 µM against MCF-7, Hela, MDA-MB-231, HL-60, and SiHa cell lines, respectively. Compound 6 was also found to exert apoptosis in HeLa cells through the activation of caspase-3. When testing the antioxidant activity of the compounds by ORAC and DPPH assays, compound 4 was found the most potent.
Acknowledgements
This work was supported by the National Research, Development and Innovation Office, Hungary (NKFIH; K119770 and K109293). A.H. acknowledges the János Bolyai fellowship of the Hungarian Academy of Sciences and the Kálmán Szász Prize.
References
[1]. I. Erlund, Nutr. Res. (2004) 24: 851-874.
[2]. M. K. Khan, et al. J. Food Compos. Anal. (2014), 33:85-104.
[3] L. Testai, et al. Front. Pharmacol. (2017) 8: art 71.