engleski

Molecular docking of quinolone-arylamidine hybrids on B-DNA dodecamer

Recently, we have synthesized and evaluated antitumor activity of a new class of hybrid molecules joining these two pharmacophores: 7- chloroquinoline and arylamidine (CQArA). (Krstulović et al., 2017). UV/Vis titrations of compounds with ds-polynucleotides suggested DNA/RNA groove binding as the dominant binding mode. Molecular docking techniques provide to understand the drug–DNA interactions in rational drug design, as well as in the mechanistic study by placing a small molecule into the binding site. In order to elucidate the binding mode between CQArA hybrids and B- DNA (d(CGCGAATTCGCG)2) (PDB: ID: 1BNA), molecular docking was performed. The Hex 8.0 performs docking using Spherical Polar Fourier Correlations. Binding energies of the two best most effective compounds against leukemia cell lines (K562 and Raji), and two new highly potent quinolone-arylamidine analogues proposed according the quantitative structure-activity relationship (QSAR) predictive model for antitumor activity. Compounds were ranked by combining the pharmacological interactions and energy-based scoring function or total energy (Etotal). Molecular docking confirmed that compounds bound preferentially in the DNA grooves. Also, antiproliferative effects can be improved with the extension of the molecules' central linker. This extension enhances the flexibility and adaptability of the molecular conformation, causing variations in the DNA binding mode. This study provide a deeper insight of interactions of CQArA hybrids with DNA. [1] L. Krstulović, I. Stolić, Jukić M., Opačak-Bernardi T., Starčević K., Bajić M., Glavaš- Obrovac Lj. Eur. J. Med. Chem. 17 (2017) 196.

docking ; DNA ; hybrid molecules ; quinoline ; arylamidine

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