Background: One of the most promising strategies to develop multi-targeted anticancer therapeutics
is to introduce to the structure of a potential drug two or more pharmacophores (functional groups or
structural fragments), which have antiproliferative, proapoptotic or antimetastatic properties acting via different
Objective: To design, synthesize and perform screening of a novel hybrid anticancer compound.
Method: A novel hybrid compound 4-[(E)-2-phenylethenesulfonamido]-N-hydroxybutanamide, combining
butanehydroxamate and styrenesulfonamide moieties, was designed, synthesized and investigated as a potent
antimetastatic and antiproliferative agent. The structure and purity of the synthesized compound were confirmed
by 1H NMR, 13C NMR, LC/MS spectroscopy and elemental analysis. The compound was screened for
the anticancer activity in vitro against HeLa and in vivo against Lewis lung carcinoma tumor, using an antitumor
metalloenzyme inhibitor GM6001 (Ilomastat, Galardin) and Pifithrin-μ as control anticancer agents.
Results: It was found that the application of our compound resulted in a high fraction of apoptotic cells in the
cell population, along with disruption in the cell cycle profile manifested as arrest of proliferative phases.
Furthermore, changes of the morphological properties (i.e., an enhancement of adhesive properties and reduction
of the nuclear-to-cytoplasm ratio) were found. The in vivo screening revealed that the compound significantly
inhibited the metastasizing process that was manifested by a reduction in the number and volume of
Conclusions: The obtained results demonstrate that our compound can serve as a base for further structure
optimization in order to design new highly-effective antimetastatic and antitumor agents.