CYTOTOXIC ACTIVITY AND MOLECULAR DOCKING STUDY OF 4- SUBSTITUTED FLAVYLIUM SALT

1^st 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

E-ADRESS / Е-АДРЕСА: dejanm@uni.kg.ac.rs, marko.zivanovic@uni.kg.ac.rs, jelena.djorovic@uni.kg.ac.rs, mdekic@np.ac.rs, marijanas14@gmail.com

DOI: 10.46793/ICCBI21.466M

ABSTRACT / САЖЕТАК:

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).

KEY WORDS / КЉУЧНЕ РЕЧИ:

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

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