Colchicine itself is a potent inhibitor of microtubule assembly, which has been applied in medicine for over a thousand years. It is currently used to treat gout, Behcet's disease, pericarditis and familial Mediterranean fever due to its anti-inflammatory and anti-vascular effects. Due of its high toxicity against normal cells, colchicine is not approved for the cancer therapy. However, development of its analogs with increased potency and reduced toxicity, which can serve as anticancer agents, is of great interest. Like in case of vinca alkaloids, vinblastine and vincristine, which are structurally very similar but are known to be effective against different types of cancer and have substantially different levels of toxicity, other colchicine site binders may be less toxic than colchicine, but still effective against cancer. Potential advantages of colchicine site binders over taxanes and vinca alkaloids include overcoming multi-drug resistance, anti-angiogenic effects as well as their structural simplicity, which ensures the relative ease of their synthesis. Numerous ligands targeting the colchicine site on tubulin have been developed, and some of them are promising candidates for chemotherapy in clinical trials. Diverse colchicine site binders contain two electron-rich (hetero)aromatic rings, predominantly polyoxygenated ones, connected by different spacer chains and rings. In accordance with this structural motif, we previously found that tetracyclic compounds containing a 5-aryl-1-benzylpyrrolidin-2-one moiety demonstrate variable cytotoxicity against a range of cancer cells. On the other hand, we also demonstrated that completely different compounds, polyoxygenated 1-arylindane derivatives and their heterocyclic analogues, also exhibited toxicity against some tumor cells. The general formulas for these two series of compounds are also given in Figure . Our ongoing interest in biologically active nitrogencontaining heterocycles and activated small ring systems in drug design led us to explore the anticancer properties of a set of novel 1,5-disubstituted pyrrolidin-2-ones 1, 2 and related pyrrolidinone based compounds 3 (Fig. ).