title: A Quinacrine Analogue Selective Against Gastric Cancer Cells: Insight from Biochemical and Biophysical Studies.
abstract: One of the earliest synthetic antimalarial drugs, quinacrine, was recently reported as interesting for the treatment of acute myeloid leukemia. Inspired by this and similar findings, we evaluated a set of quinacrine analogues against gastric (MKN-28), colon (Caco-2), and breast (MFC-7) cancer cell lines and one normal human fibroblast cell line (HFF-1). All the compounds, previously developed by us as dual-stage antimalarial leads, displayed antiproliferative activity, and one of the set stood out as selective toward the gastric cancer cell line, MKN-28. Interestingly, this compound was transported across an in vitro MKN-28 model cell line in low amounts, and approximately 80 % was trapped inside those cells. Nuclear targeting of the same compound and its interactions with calf thymus DNA were assessed through combined fluorescence microscopy, spectroscopy, and calorimetry studies, which provided evidence for the compound's ability to reach the nucleus and to interact with DNA.
authors.affiliation: UCIBIO-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007, Porto, Portugal.
authors.forename: Ana
authors.identifier: 0000-0002-5499-7112
authors.initials: A
authors.lastname: Gomes
authors.affiliation: LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007, Porto, Portugal.
authors.forename: Iva
authors.identifier: 0000-0003-2297-0086
authors.initials: I
authors.lastname: Fernandes
authors.affiliation: UCIBIO-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007, Porto, Portugal.
authors.forename: Cátia
authors.identifier: 0000-0001-9506-3781
authors.initials: C
authors.lastname: Teixeira
authors.affiliation: LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007, Porto, Portugal.
authors.forename: Nuno
authors.identifier: 0000-0002-9318-9732
authors.initials: N
authors.lastname: Mateus
authors.affiliation: CIQ-UP, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007, Porto, Portugal.
authors.forename: M J
authors.identifier: 0000-0002-2170-8003
authors.initials: MJ
authors.lastname: Sottomayor
authors.affiliation: UCIBIO-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007, Porto, Portugal.
authors.forename: Paula
authors.identifier: 0000-0002-6018-4724
authors.initials: P
authors.lastname: Gomes
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D011796:Quinacrine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D011796:Quinacrine
keywords: DNA; antiproliferation; calorimetry; cancer; spectroscopy studies