Design, Synthesis, and in vitro Evaluation of Tubulin‐Targeting Dibenzothiazines with Antiproliferative Activity as a Novel Heterocycle Building Block

We 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. Building blocks for disassembly: We synthesized a series of NH‐unsubstituted and N‐substituted dibenzothiazines, and we evaluated the antiproliferative activity against six human solid tumor cell lines. The more active compounds exhibit activity in the submicromolar range and involve targeting tubulin assembly. We highlight the dibenzothiazine core as a novel organic building block to prepare potential antitumor agents with tubulin as a cellular target.