N-Sulfonyl-aminobiaryls as Antitubulin Agents and Inhibitors of Signal Transducers and Activators of Transcription 3 (STAT3) Signaling

A series of N-sulfonyl-aminobiaryl derivatives have been examined as novel antitubulin agents. Compound 21 [N-(4′-cyano-3′-fluoro-biphenyl-2-yl)-4-methoxy-benzenesulfonamide] exhibits remarkable antiproliferative activity against four cancer cell lines (pancreatic AsPC-1, lung A549, liver Hep3B, and prostate PC-3) with a mean GI₅₀ value of 57.5 nM. Additional assays reveal that 21 inhibits not only tubulin polymerization but also the phosphorylation of STAT3 inhibition with an IC₅₀ value of 0.2 μM. Four additional compounds (8, 10, 19, and 35) are also able to inhibit this phosphorylation. This study describes novel N-sulfonyl-aminobiaryl (biaryl-benzenesulfonamides) as potent anticancer agents targeting both STAT3 and tubulin. (Chemical Equation Presented).