This effect is similar to that of microtubule destabilizers, such as colchicine, but distinct from that of paclitaxel. The frequency of microtubule catastrophes also decreased, but the effect was statistically significant only for compounds 2a and 3a. Compounds 1c, 2c, 2d and 3b exhibited a smaller, although statistically significant, effects on the microtubule growth rates, while the other tested compounds had no effect on microtubule dynamics in vitro (Fig. ). Although the 3,4,5trimethoxyaryl group (known as the A-ring of combretastatin A-4) is optimal to maintain potent activity of many colchicine site binders, compounds 1a,b did not suppress either microtubule growth rate or catastrophe frequency. Presumably, the substitution of the C=C bond as linker between two aromatic groups in combretastatin A-4 (see Fig. ) and related compounds by pyrrolidone ring influences significantly the conformational behaviour of molecule and prevent its binding to the colchicine site. The removal of one methoxy group in both phenyl rings allows compound 1c to fit into the colchicine pocket providing its weak effect on the tubulin dynamic instability.