AbstractWe prepared a series of free NH and N‐substituted dibenzonthiazines with potential anti‐tumor activity from N‐aryl‐benzenesulfonamides. A biological test of synthesized compounds (59 samples) was performed in vitro measuring their antiproliferative activity against a panel of six human solid tumor cell lines and its tubulin inhibitory activity. We identified 6‐(phenylsulfonyl)‐6H‐dibenzo[c,e][1,2]thiazine 5,5‐dioxide and 6‐tosyl‐6H‐dibenzo[c,e][1,2]thiazine 5,5‐dioxide as the best compounds with promising values of activity (overall range of 2–5.4 μM). Herein, we report the dibenzothiazine core as a novel building block with antiproliferative activity, targeting tubulin dynamics.