title: New 4-maleamic acid and 4-maleamide peptidyl chalcones as potential multitarget drugs for human prostate cancer.
abstract: OBJECTIVE
  The objective of this study was to investigate the effect of new 4-maleamic acid and 4-maleamide peptidyl chalcone derivatives against human prostate cancer in vitro and in vivo.
  
  
  METHODS
  From a series of 21 chalcones, the effects of the three best inhibitors of PC-3 and LNCaP cell viability on growth, including cell cycle changes, adhesion, migration, and cell invasion, as well as their ability to inhibit angiogenesis, clonogenic activity, and matrix metalloproteinases MMP-2 and MMP-9, were tested. The effects in vivo were studied in PC-3 and LNCaP xenografts.
  
  
  RESULTS
  Three of the examined chalcones reduced cell viability in both cell lines in a strong dose- and time-dependent manner. An inhibition of the cell cycle progress was observed. These changes were accompanied with the inhibition of cell adhesion, migration, and invasion as well as with reduced neovascularization in chick embryos, tumor colony formation, and MMP-9 activity. The in vivo results demonstrated the strong activity of these structures as inhibitors of tumor development in nude mice compared to non-treated animals.
  
  
  CONCLUSIONS
  The results suggest the multitarget efficacy of 4-maleamic acid and 4-maleamide peptidyl chalcones against human prostate cancer cells and emphasize the potential therapeutic relevance of these compounds.
authors.affiliation: Department of Urology, University Hospital Charité, Schumannstrasse 20/21, 10117, Berlin, Germany.
authors.forename: Juan
authors.initials: J
authors.lastname: Rodrigues
authors.forename: Claudia
authors.initials: C
authors.lastname: Abramjuk
authors.forename: Luis
authors.initials: L
authors.lastname: Vásquez
authors.forename: Neira
authors.initials: N
authors.lastname: Gamboa
authors.forename: José
authors.initials: J
authors.lastname: Domínguez
authors.forename: Bianca
authors.initials: B
authors.lastname: Nitzsche
authors.forename: Michael
authors.initials: M
authors.lastname: Höpfner
authors.forename: Radostina
authors.initials: R
authors.lastname: Georgieva
authors.forename: Hans
authors.initials: H
authors.lastname: Bäumler
authors.forename: Carsten
authors.initials: C
authors.lastname: Stephan
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.forename: Michael
authors.initials: M
authors.lastname: Lein
authors.forename: Anja
authors.initials: A
authors.lastname: Rabien
mesh_terms: D000577:Amides / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008298:Maleates / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D047188:Chalcones; D008298:Maleates; C008311:maleamic acid