MS05-P09 Structural investigation of the interaction between Combretastatin A-4 analogues with benzoxazolone scaffold and αβ-tubulinA series of 70 new Combretastatin A-4 (CA4) analogues have been synthesized by modified Wittig reaction . The compounds were tested in vitro for cell growth inhibition and the ability to induce apoptosis against HepG2, EA.hy926 and K562 cell line. The most active compounds were further tested against HT-29, Colon-26, A-549, MCF-7, MDA-MD-231, MCF-10A, HaCaT and NHEK lines. The new compounds have been characterized by single crystal diffraction and preliminary data about the interaction of the most active CA-4 analogues has been obtained using fluorescence displacement assay. The crystallization of selected analogues with αβ-tubulin-RSB complex suggested that interaction might occur at different sites though the “small molecules” are structurally very alike (Fig. 1).
Figure 1. General scheme of synthesized analogues a), ORTEP view of the molecule of compound SZ16 present in the asymmetric unit  b) and possible interaction (binding) sites of the analogues with αβ-tubulin dimmer.
Acknowledgments: The authors would like to thank the Bulgarian National Science Found project H19/13 2017.
Gerova, M. S., et al. (2016) Eur. J. Med. Chem. 120, 121-133.Keywords: Stilbene, Tubulin binding, Anticancer agents