Design,Synthesis, and in vitro Evaluation of Tubulin-Targeting Dibenzothiazines with Antiproliferative Activity as a Novel Heterocycle Building Block |
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| Authors: | Dr Walter D Guerra Dr Daniel Lucena-Agell Rafael Hortigüela Prof Roberto A Rossi Dr J Fernando Díaz Prof José M Padrón Dr Silvia M Barolo |
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| Affiliation: | 1. Instituto de Investigaciones en Físico Química de Córdoba, Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, X5000HUA Córdoba, Argentina;2. Centro de Investigaciones Biológicas Margarita Salas (CIB-MS, CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain;3. BioLab, Instituto Universitario de Bio-Orgánica Antonio González (IUBO-AG), Universidad de La Laguna, C/Astrofísico Francisco Sánchez 2, 38206 La Laguna, Spain |
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| 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-dibenzoc,e]1,2]thiazine 5,5-dioxide and 6-tosyl-6H-dibenzoc,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. |
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| Keywords: | Antiproliferation dibenzothiazines drug design sulfonamides tubulin inhibitors |
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