Design, Synthesis, and In Vitro Evaluation of Tubulin-targeting Dibenzothiazines with Antiproliferative Activity as Novel Heterocycle Building Block

HORTIGÜELA RAFAEL; JOSE M. PADRÓN; LUCENA-AGELL DANIEL; DIAZ, J. FERNANDO ; GUERRA, WALTER D.; ROSSI, ROBERTO A.; BAROLO, SILVIA M.

CHEMMEDCHEM

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2021 vol. 16 p. 3003 - 3016

1860-7179

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.