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

Abstract

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.

• Authors: Walter D Guerra, Daniel Lucena-Agell, Rafael Hortigüela, Roberto A Rossi, J Fernando Díaz, José M Padrón, Silvia M Barolo
• Journal: ChemMedChem (ChemMedChem) Vol. 16 Issue 19 Pg. 3003-3016 (10 06 2021) ISSN: 1860-7187 [Electronic] Germany
• PMID: 34231318 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Wiley-VCH GmbH.

Chemical References

• Antineoplastic Agents
• Heterocyclic Compounds
• Thiazines
• Tubulin
• Tubulin Modulators

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Brain (drug effects, metabolism)
• Cattle
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Design
• Drug Screening Assays, Antitumor
• Heterocyclic Compounds (chemical synthesis, chemistry, pharmacology)
• Humans
• Molecular Structure
• Structure-Activity Relationship
• Thiazines (chemistry, pharmacology)
• Tubulin (metabolism)
• Tubulin Modulators (chemical synthesis, chemistry, pharmacology)