title: Synthesis and pro-apoptotic effects of new sulfonamide derivatives via activating p38/ERK phosphorylation in cancer cells.
abstract: Herein, the compounds bearing sulfonamide fragment such as N-(2-amino-5-benzoylphenyl)-4-nitrobenzene sulfonamide hydrochloride (1), N-(quinolin-8-yl)-4-nitro-benzenesulfonamide hydrochloride (2), N-(pyridine-2-ylmethyl)-4-nitro-benzenesulfonamide hydrochloride (3) were synthesized by the reaction of 3,4-diaminobenzophenone, 8-aminoquinoline or 2-picoylamine and 4-nitrobenzensulfonyl chloride, respectively. The structures of the newly synthesized compounds were elucidated on the basis of elemental and spectral analyses. All the prepared compounds were evaluated for their in vitro anti-cancer activity against various cancer cell lines and to explore the underlying molecular mechanisms involved in this process. In vitro cytotoxic activities of the compounds were screened against human hepatocellular (HepG2), breast (MCF-7) and colon (Colo-205) cancer cell lines by MTT assay, mRNA expression of genes with qPCR and phosphorylation of p38 and ERK1/2 with Western blot. Tested compounds could significantly reduce cell proliferation and induced mRNA expression of pro-apoptotic genes; caspase 3, caspase 8 and caspase 9. Activation of these apoptotic genes probably is mediated by activation of p38.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy and.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Cumaoglu
authors.forename: Serkan
authors.initials: S
authors.lastname: Dayan
authors.forename: Asli Ozge
authors.initials: AO
authors.lastname: Agkaya
authors.forename: Zehra
authors.initials: Z
authors.lastname: Ozkul
authors.forename: Nilgun Kalaycioglu
authors.initials: NK
authors.lastname: Ozpozan
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; D013449:Sulfonamides; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Apoptosis; MAPK; cancer; caspases; sulfonamide derivatives