title: Biological screening of novel derivatives of valproic acid for anticancer and antiangiogenic properties.
abstract: BACKGROUND
  Valproic acid (VPA) is a potent anticancer and antiangiogenic agent. However, design and synthesis of chemical derivatives with improved antiangiogenic and anticancer activities are still necessary. In this study a library of novel derivatives of VPA was synthesized and tested.
  
  
  METHODS
  A human liver cancer cell line (HepG2) and a human normal embryonic kidney cell line (HEK 293) were exposed to various concentrations of VPA derivatives for 24 hours and cell viability was checked by MTT colorimetric assay. Anti-angiogenic properties were evaluated in transgenic zebrafish embryos.
  
  
  RESULTS
  N-valproylglycine derivatives suppressed survival almost 70% (p value 0.001) in HepG2 cells but only 10-12% in HEK 293 cells (p value 0.133). They also suppressed angiogenic blood vessel formation by 80% when used between 2-20 μM in zebrafish embryos. Valproic acid hydrazides showed moderate level of anticancer activity by affecting 30-50% (p value 0.001) of cell viability in HepG2 cells and 8-10% in HEK293 cells (p value 0.034).
  
  
  CONCLUSIONS
  The majority of compounds in this study showed potent and stronger antiangiogenic and anticancer activity than VPA. They proved selectively toxic to cancer cells and safer for normal cells. Moreover, these compounds inhibited developmental angiogenesis in zebrafish embryos. Based on the fact that liver is a highly vascularized organ, in case of liver carcinoma these compounds have the potential to target the pathological angiogenesis and could be an effective strategy to treat hepatocellular carcinoma.
authors.affiliation: Bioproducts Research Chair, Department of Zoology, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia E-mail : fmuhammad@ksu.edu.sa.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Farooq
authors.forename: Ayman
authors.initials: A
authors.lastname: El-Faham
authors.forename: Sherine N
authors.initials: SN
authors.lastname: Khattab
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Elkayal
authors.forename: Mahmoud F
authors.initials: MF
authors.lastname: Ibrahim
authors.forename: Nael Abu
authors.initials: NA
authors.lastname: Taha
authors.forename: Almohannad
authors.initials: A
authors.lastname: Baabbad
authors.forename: Mohammad A M
authors.initials: MA
authors.lastname: Wadaan
authors.forename: Ezaat A
authors.initials: EA
authors.lastname: Hamed
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D000927:Anticonvulsants / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D015394:Molecular Structure; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D014635:Valproic Acid / Q000494:pharmacology*; D015027:Zebrafish
chemical_list: D020533:Angiogenesis Inhibitors; D000927:Anticonvulsants; D014635:Valproic Acid