RESUMEN

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.

Asunto(s)

Antineoplásicos/farmacología , Diseño de Fármacos , Compuestos Heterocíclicos/farmacología , Tiazinas/farmacología , Moduladores de Tubulina/farmacología , Tubulina (Proteína)/metabolismo , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Bovinos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Compuestos Heterocíclicos/síntesis química , Compuestos Heterocíclicos/química , Humanos , Estructura Molecular , Relación Estructura-Actividad , Tiazinas/química , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/química

RESUMEN

Novel approaches for N- and O-desulfonylation under room temperature (rt) and transition-metal-free conditions have been developed. The first methodology involves the transformation of a variety of N-sulfonyl heterocycles and phenyl benzenesulfonates to the corresponding desulfonylated products in good to excellent yields using only KOtBu in dimethyl sulfoxide (DMSO) at rt. Alternately, a visible light method has been used for deprotection of N-methyl-N-arylsulfonamides with Hantzsch ester (HE) anion serving as the visible-light-absorbing reagent and electron and hydrogen atom donor to promote the desulfonylation reaction. The HE anion can be easily prepared in situ by reaction of the corresponding HE with KOtBu in DMSO at rt. Both protocols were further explored in terms of synthetic scope as well as mechanistic aspects to rationalize key features of desulfonylation processes. Furthermore, the HE anion induces reductive dehalogenation reaction of aryl halides under visible light irradiation.

RESUMEN

A new and general synthetic route to prepare dibenzosultams is here reported. This approach involves the synthesis of N-aryl-2-halobenzenesulfonamides (3), followed by intramolecular C-C photoinduced arylation under soft conditions without the use of "Transition Metal". The photostimulated reactions exhibit very good tolerance to different substituent groups with good to excellent isolated yields (42-98%) of products. Moreover, it is shown that LED (λ = 395 nm) is an efficient light energy source to initiate efficiently the reactions. Theoretical inspection of the mechanism was made to probe the involvement of the radical-anion SRN1 process.