Synthesis and Antitumor Activity of Some Substituted Indazole Derivatives. Issue 6 (19th February 2014)

• Record Type: Journal Article
• Authors: Abbassi, Najat; Rakib, El Mostapha; Chicha, Hakima; Bouissane, Latifa; Hannioui, Abdellah; Aiello, Cinzia; Gangemi, Rosaria; Castagnola, Patrizio; Rosano, Camillo; Viale, Maurizio
• Is Part Of: Archiv der Pharmazie. Volume 347:Issue 6(2014:Jun.)
• Page Start: 423
• Page End: 431
• Publication Date: 2014-02-19
• Subjects: Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201300390
• Languages: English
• ISSNs: 0365-6233

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ardp201300390-sec-0001" sec-type="section"> <p>Some new <italic>N</italic>‐[6‐indazolyl]arylsulfonamides and <italic>N</italic>‐[alkoxy‐6‐indazolyl]arylsulfonamides were prepared by the reduction of 2‐alkyl‐6‐nitroindazoles with SnCl<sub>2</sub> in different alcohols, followed by coupling the corresponding amine with arylsulfonyl chlorides in pyridine. The newly synthesized compounds were evaluated for their antiproliferative and apoptotic activities against two human tumor cell lines: A2780 (ovarian carcinoma) and A549 (lung adenocarcinoma). Preliminary <italic>in vitro</italic> pharmacological studies revealed that <italic>N</italic>‐(2‐allyl‐2<italic>H</italic>‐indazol‐6‐yl)‐4‐methoxybenzenesulfonamide <bold>4</bold> and <italic>N</italic>‐[7‐ethoxy‐2‐(4‐methyl‐benzyl)‐2<italic>H</italic>‐indazol‐6‐yl]‐4‐methyl‐benzenesulfonamide <bold>9</bold> exhibited significant antiproliferative activity against the A2780 and A549 cell lines with IC<sub>50</sub> values in the range from 4.21 to 18.6 µM, and also that they trigger apoptosis in a dose‐dependent manner. Furthermore, both active compounds were able to cause an arrest of cells in the G2/M phase of the cell cycle, typical but not exclusive of tubulin interacting agents, although only infrequent interactions with the microtubule network were observed by immunofluorescence microscopy, while docking analysis showed a possible different behavior between the two active compounds.</p> </sec> </abstract>