title: Anti-tumor activity of novel biisoquinoline derivatives against breast cancers.
abstract: Breast cancer is classified into three groups according to its expression of hormone/growth factor receptors: (i) estrogen receptor (ER) and progesterone receptor (PR)-positive; (ii) human epidermal growth factor receptor 2 (HER2)-positive; and (iii) ER, PR, and HER2-negative (triple-negative). A series of methoxy-substituted biisoquinoline compounds have been synthesized as a potential chemotherapeutic agent for the triple-negative breast cancers which are especially challenging to manage. Structure activity relationship study revealed that rigid 6,6'-dimethoxy biisoquinoline imidazolium compound (1c, DH20931) exhibited the significant growth inhibitory effects on both triple-positive and triple-negative human breast cancer cell lines with IC50 in the range of 0.3-3.9 μM. The 1c (DH20931) is more potent than structurally related noscapine for growth inhibition of MCF7 cell line (IC50=1.3 vs 57 μM) and MDA-MB231 cell line (IC50=3.9 vs 64 μM).
authors.affiliation: Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Aruna S
authors.initials: AS
authors.lastname: Jaiswal
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Hirsch-Weil
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA.
authors.forename: Erick R
authors.initials: ER
authors.lastname: Proulx
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA; Research Institute for Solar and Sustainable Energies (RISE), School of Materials Science & Engineering, Gwangju Institute of Science and Technology, 123 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712, Republic of Korea. Electronic address: shong@gist.ac.kr.
authors.forename: Sukwon
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USA. Electronic address: snarayan@ufl.edu.
authors.forename: Satya
authors.initials: S
authors.lastname: Narayan
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007546:Isoquinolines
keywords: Biisoquinoline; Breast cancer; MCF7; MDA-MB231; Noscapine