title: Aromatic sulfonamides containing a condensed piperidine moiety as potential oxidative stress-inducing anticancer agents.
abstract: A 30-membered piperidine ring-fused aromatic sulfonamide library was synthetized, including N-arylsulfonyl 1,2,3,4-tetrahydroquinolines, 1,2,3,4-tetrahydroisoquinolines and 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoles. The compounds induced oxidative stress and glutathione depletion in HT168 melanoma and K562 leukemia cells and in micromolar concentrations exerted cytotoxic effects. Among the tested sulfonamides, compounds 21, 22, 23, 35 and 41 exhibited 100% cytotoxic effects with low (< 10 µM) EC50 values on K562 cells. The cytotoxicity of lead compound 22 was investigated in 24 different cancer cell lines, and it was found to be active against leukemia, melanoma, glioblastoma, and liver, breast and lung cancer cells, as confirmed by classical biochemical and holographic microscopic analyses.
authors.affiliation: AVIDIN Ltd. Alsó kikötö sor 11, Szeged, H-6726, Hungary. laszlo@avidinbiotech.com.
authors.forename: Ramóna
authors.initials: R
authors.lastname: Madácsi
authors.forename: Iván
authors.initials: I
authors.lastname: Kanizsai
authors.forename: Liliána Z
authors.initials: LZ
authors.lastname: Fehér
authors.forename: Márió
authors.initials: M
authors.lastname: Gyuris
authors.forename: Béla
authors.initials: B
authors.lastname: Ozsvári
authors.forename: András
authors.initials: A
authors.lastname: Erdélyi
authors.forename: János
authors.initials: J
authors.lastname: Wölfling
authors.forename: László G
authors.initials: LG
authors.lastname: Puskás
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects*; D010880:Piperidines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D013449:Sulfonamides; C032727:piperidine