title: Synthesis and antitumor activity of some substituted indazole derivatives.
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.
authors.affiliation: Laboratory of Organic and Analytical Chemistry, Faculty of Sciences and Technology, University Sultan Moulay Slimane, Béni-Mellal, Morocco.
authors.forename: Najat
authors.initials: N
authors.lastname: Abbassi
authors.forename: El Mostapha
authors.initials: el M
authors.lastname: Rakib
authors.forename: Hakima
authors.initials: H
authors.lastname: Chicha
authors.forename: Latifa
authors.initials: L
authors.lastname: Bouissane
authors.forename: Abdellah
authors.initials: A
authors.lastname: Hannioui
authors.forename: Cinzia
authors.initials: C
authors.lastname: Aiello
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gangemi
authors.forename: Patrizio
authors.initials: P
authors.lastname: Castagnola
authors.forename: Camillo
authors.initials: C
authors.lastname: Rosano
authors.forename: Maurizio
authors.initials: M
authors.lastname: Viale
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007191:Indazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008856:Microscopy, Fluorescence; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles
keywords: 2-Alkyl-6-nitroindazoles; Antiproliferative activity; Apoptosis; N-[6-Indazolyl]arylsulfonamides; SnCl2/alcohols