1st International Conference on Chemo and BioInformatics, ICCBIKG  2021, (466-469)

AUTHOR(S) / АУТОР(И): Dejan A. Milenković, Marko N. Živanović, Milan S. Dekić, Marijana Stanojević Pirković, Jelena R. Đorović Jovanović


Download Full Pdf   

DOI: 10.46793/ICCBI21.466M


In the present manuscript, the cytotoxic activity of flavylium cation substituted at 4- position with phenyl (FC-4Ph) was tested to two cells lines (human colorectal carcinoma, HCT-116, and human fibroblast lung, MRC-5). In vitro cytotoxicity experiments were performed to elucidate the possible anticancer activity of tested substance. Investigated compound did not show cytotoxic effect on HCT-116 after 24 h, while after 72 h exerted significant effect. A significant selectivity towards colorectal carcinoma cells was observed. On the other hand, this compound did not show any effect on MRC-5 cell line. The molecular interactions between receptor tyrosine kinase (RTK) and title compound was examined. The crystal structure of investigated receptor RTK was downloaded from Protein Data Bank. The native bound ligand ((E)-[4-(3,5-difluorophenyl)-3H-pyrrolo[2,3-b]pyridin-3-ylidene](3- methoxyphenyl)methanol was extracted from receptor and binding pocket analysis was performed. Re-docking was carried out with the FC-4Ph in order to generate the same docking pose as found in co-crystallized form of receptor. The obtained results of revealed that investigated compound binds at the same binding pockets to RTK, as well as native bound ligand, by weak non-covalent interactions. The most prominent interactions are hydrogen bonds, π-alkyl, and π-π interactions. The preliminary results suggest that investigated compound showed good binding affinity against RTK, as evident from the free binding energy (ΔGbind in kJ/mol).


cytotoxic activity, molecular docking, flavylium cation, receptor tyrosine kinase, free binding energy


  • N. R. Song, H. Yang, J. Park, J.Y. Kwon, N.J. Kang, Y.S. Heo, K.W. Lee, H.J. Lee, Cyanidin suppresses neoplastic cell transformation by directly targeting phosphatidylinositol 3-kinase, Food Chemistry, 133 (2012) 658–664.
  • K. D. Vu, H. Carlettini, J. Bouvet, J. Côté, G. Doyon, J.F. Sylvain, M. Lacroix, Effect of different cranberry extracts and juices during cranberry juice processing on the antiproliferative activity against two colon cancer cell lines, Food Chemistry. 132 (2012) 959–967.
  • F. Pina, V. Petrov, C.A.T. Laia, Photochromism of flavylium systems. An overview of a versatile multistate system, Dyes and Pigments, 92 (2012) 877–889.
  • C. García-Viguera, P. Bridle, Influence of structure on colour stability of anthocyanins and flavylium salts with ascorbic acid, Food Chemistry 64 (1999) 21–26.
  • E. Zwick , J. Bange, A. Ullrich, Receptor tyrosine kinase signalling as a target for cancer intervention strategies, Endocrine-Related Cancer 8 (2001) 161–173.
  • M. Dekić, R. Kolašinac, N. Radulović, B. Šmit, D. Amić, K. Molčanov, D. Milenković, Z. Marković, Synthesis and theoretical investigation of some new 4-substituted flavylium salts, Food Chemisty 229 (2017) 688-694.
  • E. H. Avdović, D.S. Dimić, J.M. Dimitrić Marković, N. Vuković, M. Radulović, M.N. Živanović, N.D. Filipović, J.R. Đorović, S.R. Trifunović, Z.S. Marković, Spectroscopic and theoretical investigation of the potential anti-tumor and anti-microbial agent, 3-(1-((2- hydroxyphenyl)amino)ethylidene)chroman-2,4-dione, Spectrochimica Acta Part A: Molecular and Biomolecular 206 (2019) 421–429.
  • M. S. Valdés-Tresanco, M.E. Valdés-Tresanco, P.A. Valiente, E. Moreno, AMDock: a versatile graphical tool for assisting molecular docking with Autodock Vina and Autodock4, Biology Direct, 15 (2020) 1–12.
  • BIOVIA, Dassault Systèmes, Discovery studio modeling environment, release 2017, Dassault Systèmes, San Diego, 2017.
  • G. M. Morris, R. Huey, W. Lindstrom, M.F. Sanner, R.K. Belew, D.S. Goodsell, A.J. Olson, AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility, Journal of Computational Chemistry, 30 (2009) 2785–2791.