Diaryl ethers represent an important class of synthetic compounds recognized as potential anticancer drugs. Experimental and pre-clinical models have demonstrated that a number of these compounds elicit outstanding anticancer activity through the significant inhibition of tubulin assembly accompanied by potent antiproliferative activity. Moreover, the diaryl ether scaffold is found in a number of natural products and biologically important molecules, such as vancomycin and piperazinomycin. As a result of our continuing studies aimed at the discovery and development of potential anticancer agents, herein we report the synthesis, cytotoxic activities of a series of nlovel diaryl ethers. Diaryl ether (1) was synthesized via Ullmann-type coupling. Palladium(II) acetate catalyzed O-arylation reactions have been carried out in non-polar solvent and used K3PO4 as the base. Saponification in ethanolic NaOH solution afforded the acid form (2). Both compound 1 and 2 were shown selective cytotoxic activity against A549 (Human lung adenocarcinoma epithelial cell line) with the IC50 values of 2.1 μM and 12.3 μM, respectively.
