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Synthesis and Antitumor Activity of Some Substituted Indazole Derivatives
Author(s) -
Abbassi Najat,
Rakib El Mostapha,
Chicha Hakima,
Bouissane Latifa,
Hannioui Abdellah,
Aiello Cinzia,
Gangemi Rosaria,
Castagnola Patrizio,
Rosano Camillo,
Viale Maurizio
Publication year - 2014
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201300390
Subject(s) - chemistry , alkoxy group , apoptosis , indazole , cell culture , stereochemistry , a549 cell , in vitro , cell cycle , docking (animal) , cell cycle checkpoint , amine gas treating , alkyl , biochemistry , biology , organic chemistry , medicine , nursing , genetics
Some new N ‐[6‐indazolyl]arylsulfonamides and N ‐[alkoxy‐6‐indazolyl]arylsulfonamides were prepared by the reduction of 2‐alkyl‐6‐nitroindazoles with SnCl 2 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‐2 H ‐indazol‐6‐yl)‐4‐methoxybenzenesulfonamide 4 and N ‐[7‐ethoxy‐2‐(4‐methyl‐benzyl)‐2 H ‐indazol‐6‐yl]‐4‐methyl‐benzenesulfonamide 9 exhibited significant antiproliferative activity against the A2780 and A549 cell lines with IC 50 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.