Indolo[2,3-<i>e</i>]benzazocines and indolo[2,3-<i>f</i>]benzazonines and their copper(<scp>ii</scp>) complexes as microtubule destabilizing agents
Christopher Wittmann, Orsolya Dömötör, Irina Kuznetcova, Gabriella Spengler, Jóhannes Reynisson, Lauren Holder, Gavin J. Miller, Éva A. Enyedy, Ruoli Bai, Ernest Hamel, Vladimir B. Arion
Abstract
values in the low micromolar to sub-micromolar concentration range, while some of them (HL1, HL5 and HL6, 1, 2 and 6) showed remarkable selectivity towards malignant cell lines. Ethidium bromide displacement studies provided evidence that DNA is not the primary target for these drugs. Rather, inhibition of tubulin assembly is likely the underlying mechanism responsible for their antiproliferative activity. Tubulin disassembly experiments showed that HL1 and 1 are effective microtubule destabilizing agents binding to the colchicine site. This was also confirmed by molecular modelling investigations. To the best of our knowledge, complex 1 is the first reported transition metal complex to effectively bind to the tubulin-colchicine pocket.