Synthesis and antitumor activity of some substituted indazole derivatives

Najat Abbassi, El Mostapha Rakib, Hakima Chicha, Latifa Bouissane, Abdellah Hannioui, Cinzia Aiello, Rosaria Gangemi, Patrizio Castagnola, Camillo Rosano, Maurizio Viale

Research output: Contribution to journalArticlepeer-review

Abstract

Some new N-[6-indazolyl]arylsulfonamides and N-[alkoxy-6-indazolyl] arylsulfonamides were prepared by the reduction of 2-alkyl-6-nitroindazoles with SnCl2 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 in vitro pharmacological studies revealed that N-(2-allyl-2H-indazol-6-yl)-4-methoxybenzenesulfonamide 4 and N-[7-ethoxy-2-(4-methyl-benzyl)-2H-indazol-6-yl]-4-methyl-benzenesulfonamide 9 exhibited significant antiproliferative activity against the A2780 and A549 cell lines with IC50 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. Some new N-[6-indazolyl]arylsulfonamides were synthesized and screened against two human tumor cell lines, A2780 and A549. Most of the new compounds, and especially compounds 4 and 9, showed promising anticancer activities against both cell lines.

Original languageEnglish
Pages (from-to)423-431
Number of pages9
JournalArchiv der Pharmazie
Volume347
Issue number6
DOIs
Publication statusPublished - 2014

Keywords

  • 2-Alkyl-6-nitroindazoles
  • Antiproliferative activity
  • Apoptosis
  • N-[6-Indazolyl]arylsulfonamides

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmaceutical Science
  • Medicine(all)

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