title: SAR-guided development and characterization of a potent antitumor compound toward B-cell neoplasms with no detectable cytotoxicity toward healthy cells.
abstract: Acute hematological diseases (leukemias and aggressive lymphomas) can be cured in approximately half of the patients, while the other patients die from their disease. Chronic leukemias and indolent lymphomas can be well controlled for years in most cases. However, the cure rate of these patients is low and the course of the disease is characterized by frequent recurrence. Therefore, novel agents for monotherapies or combination therapies still need to be explored. The presented study describes the identification of the chalcone derivative 15 on different types of human malignant cells of the lymphoid and myeloid lineage. Further experiments performed with compound 15 on peripheral blood mononuclear cells (PBMCs) of chronic lymphocytic leukemia (CLL) patients clearly stated a higher cytotoxicity in PBMC from CLL patients compared to healthy donors (HD). The newly identified chalcone derivative 15 showed a higher therapeutic potential than fludarabine, a drug already in use in lymphoma treatment.
authors.affiliation: Department of Medicinal Chemistry, University of Vienna , Althanstrasse 14, 1090 Vienna, Austria.
authors.forename: Gerda
authors.initials: G
authors.lastname: Brunhofer-Bolzer
authors.forename: Trang
authors.initials: T
authors.lastname: Le
authors.forename: Nils
authors.initials: N
authors.lastname: Dyckmanns
authors.forename: Hanna A
authors.initials: HA
authors.lastname: Knaus
authors.forename: Clemens
authors.initials: C
authors.lastname: Pausz
authors.forename: Patricia
authors.initials: P
authors.lastname: Freund
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jäger
authors.forename: Thomas
authors.initials: T
authors.lastname: Erker
authors.forename: Katrina
authors.initials: K
authors.lastname: Vanura
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents