title: Identification of novel 2-(1H-indol-1-yl)-benzohydrazides CXCR4 ligands impairing breast cancer growth and motility.
abstract: BACKGROUND
  Stromal-derived-factor-1 (SDF-1) and the G-protein-coupled receptor CXCR4 are involved in several physiological and pathological processes including breast cancer spread and progression. Several CXCR4 antagonists have currently reached advanced development stages as potential therapeutic agents for different diseases.
  
  
  RESULTS
  A small series of novel CXCR4 ligands, based on a 2-(1H-indol-1-yl)-benzohydrazide scaffold, has been designed and synthesized. The interaction with CXCR4-active site was predicted by molecular docking and confirmed by whole cell-based [(125)I]-SDF-1 ligand competition binding assays. One of the synthesized compounds was particularly active in blocking SDF-1-induced breast cancer cell motility, proliferation and downstream signaling activation in different breast cancer cell models and coculture systems.
  
  
  CONCLUSIONS
  The newly synthesized compounds represent suitable leads for the development of innovative therapeutic agents targeting CXCR4.
authors.affiliation: Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, Via P Bucci, 87036 Rende (Cs), Italy.
authors.forename: Fedora
authors.initials: F
authors.lastname: Grande
authors.affiliation: Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, Via P Bucci, 87036 Rende (Cs), Italy.
authors.forename: Ines
authors.initials: I
authors.lastname: Barone
authors.affiliation: Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, Via P Bucci, 87036 Rende (Cs), Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Aiello
authors.affiliation: School of Pharmacy & Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff, CF10 3NB, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancale
authors.affiliation: School of Pharmacy & Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff, CF10 3NB, UK.
authors.forename: Michela
authors.initials: M
authors.lastname: Cancellieri
authors.affiliation: Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, Via P Bucci, 87036 Rende (Cs), Italy.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Badolato
authors.affiliation: Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, Via P Bucci, 87036 Rende (Cs), Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Chemi
authors.affiliation: Centro Sanitario, University of Calabria, Via P Bucci, 87036 Rende (Cs), Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Giordano
authors.affiliation: Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, Via P Bucci, 87036 Rende (Cs), Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vircillo
authors.affiliation: Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, Via P Bucci, 87036 Rende (Cs), Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bonofiglio
authors.affiliation: Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, Via P Bucci, 87036 Rende (Cs), Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Garofalo
authors.affiliation: Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, Via P Bucci, 87036 Rende (Cs), Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Andò
authors.affiliation: Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, Via P Bucci, 87036 Rende (Cs), Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Catalano
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015195:Drug Design; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D008024:Ligands; D062105:Molecular Docking Simulation; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D006834:Hydrazines; D008024:Ligands; D019718:Receptors, CXCR4; C029424:hydrazine
keywords: CXCR4 antagonists; breast cancer; docking simulation; endocrine resistance; tumor microenvironment