ABSTRACT
Recently, it has been reported that compounds bearing a sulfonamide moiety possess many types of biological activities, including anticancer activity. The present work reports the synthesis and antiproliferative evaluation of some N-(6(4)-indazolyl)benzenesulfonamides and 7-ethoxy-N-(6(4)-indazolyl)benzenesulfonamides. All compounds were evaluated for their in vitro antiproliferative activity against three tumor cell lines: A2780 (human ovarian carcinoma) A549 (human lung adenocarcinoma) and P388 (murine leukemia). The results indicated that sulfonamides 2c, 3c, 6d, 8, 13, 3b and 16 were endowed with a pharmacologically interesting antiproliferative activity with compounds 2c and 3c showing the lower IC(50) (from 0.50 ± 0.09 to 1.83 ± 0.52 µM and from 0.58 ± 0.17 to 5.83 ± 1.83 µM, respectively). Moreover, these indazoles were able to trigger apoptosis through the upregulation of the typical apoptosis markers p53 and bax. As regard to the hypothetic targets of these compounds, a preliminary docking analysis showed that all compounds seemed to interact with ß-tubulin, in particular compound 3b that showed the lower Ki. The cytofluorimetric analysis of the cell cycle phases indicates that all compounds, when administered at their IC(75), caused a block in the G2/M phase of the cell cycle with the generation of subpopulations of cells with a number of chromosome >4n. When the IC(50)s were applied we observed a prevalent block in the G0/G1 phase except for compounds 16 and 8 where a partial G2/M block was present with a concomitant decrease of cells in the G0/G1 and S phases of the cell cycle. Altogether these results suggest a possible, but not exclusive, interaction with microtubules.
Subject(s)
Antineoplastic Agents/chemical synthesis , Indazoles/chemical synthesis , Sulfonamides/chemical synthesis , Tubulin/chemistry , Animals , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Flow Cytometry , G1 Phase/drug effects , G2 Phase Cell Cycle Checkpoints/drug effects , Humans , Indazoles/pharmacology , Inhibitory Concentration 50 , Kinetics , Mice , Microtubules/drug effects , Molecular Docking Simulation , Polyploidy , Resting Phase, Cell Cycle/drug effects , Structure-Activity Relationship , Sulfonamides/pharmacology , Tubulin/metabolismABSTRACT
La diapneusie est une tumeur benigne correspondant a une hyperplasie fibro-epitheliale de forme nodulaire avec une muqueuse de recouvrement d'aspect normal. Elle siege preferentiellement sur le bord de la langue; et sur la face interne des muqueuses jugales. Elle est secondaire a un tic de succion; la diapneusie est toujours en regard d'un espace edente. Elle est toujours benigne mais elle recidive tant que l'etiologie n'a pas ete eliminee .A travers des cas cliniques; cette presentation; a pour objectif d'eclairer le praticien sur le diagnostic facile de cette tumeur et que de comparer les differentes techniques therapeutiques
