Csámpai, Antal

Girst, Gábor

Hunyadi, Attila

Jenei, Tamás

Latif, Ahmed

Vágvölgyi, Máté

Zupkó, István

Latif Ahmed

Vágvölgyi Máté

Girst Gábor

Jenei Tamás

Zupkó István

Csámpai Antal

Hunyadi Attila

University of Szeged

Trends in Natural Product Research – PSE Young Scientists’ Meeting Budapest, June 19th-21th, 2019 80  SL-33 doi: 10.14232/tnpr.2019.sl33  In vitro antitumor activity of protoflavone-based hybrid compounds on human gynecological cancer cell lines  Ahmed Latif1,2,*, Máté Vágvölgyi1, Gábor Girst1, Tamás Jenei3, István Zupkó2, Antal Csámpai3 and Attila Hunyadi1  1 Institute of Pharmacognosy, University of Szeged, Szeged. Hungary 2 Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged. Hungary 3 Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary *E-mail: alhussainy53@yahoo.com   Protoflavones are rare and unusual flavonoid derivatives having a non-aromatic B-ring; in nature, they can most typically be found in certain genera of fern species. Protoflavones are promising, natural anticancer agents, and their in vitro and in vivo activity inspired the synthesis of many semi- and total synthetic analogs [1]. In the current study, our aim was to evaluate the antitumor potential of a set of new hybrid compounds, each containing a protoflavone and a chalchone or ferrocene fragment. Four new compounds were prepared and studied for their in vitro antitumor activity against four gynecological human cancer cell lines including HeLa and SiHa (cervical), and MCF-7 and MDA-MB-231 (breast) cancer cells, with cisplatin as a positive control. When testing by MTT assay, the compounds showed strong antiproliferative activities with IC50 values in the low-medium nanomolar range. To quantitatively evaluate pharmacological benefit gained by the coupling, bioactivity of each compound was further analyzed in a virtual combination study, i.e. considering it as an interaction of a 1:1 ratio mixture of the corresponding protoflavone and chalchone building block. The most potent compound demonstrated an IC50 value of 153 nM against SiHa cells, representing a combination index value of 0.10 (i.e. very strong synergism) for the two separate fragments. This compound was found to induce apoptosis in MDA-MB-231 and SiHa cells through the significant increase in the hypodiploid (sub G1) population as evidenced by cell cycle analysis and induced the activation of caspase-3. Our study highlights the pharmacological potential of protoflavone-based hybrid compounds and demonstrates that these hybrids are much more than a simple addition of their chemical elements.   Acknowledgements This work was supported by the National Research, Development and Innovation Office, Hungary (NKFIH; K119770, K109293, and K129037). A.H. acknowledges the János Bolyai fellowship of the Hungarian Academy of Sciences, the UNKP-18-4 New National Excellence Program of the Ministry of Human Capacities and the Kálmán Szász Prize.  Reference [1] Hunyadi A et al. Phytochem Rev. 2014; 13:69-77.  

In vitro antitumor activity of protoflavone-based hybrid compounds on human gynecological cancer cell lines : [abstract]

http://acta.bibl.u-szeged.hu/62010/1/ysm_2019_080.pdf

In vitro antitumor activity of protoflavone-based hybrid compounds on human gynecological cancer cell lines

In vitro antitumor activity of protoflavone-based hybrid compounds on human gynecological cancer cell lines

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