title: Synthesis and biological activity of Schiff base series of valproyl, N-valproyl glycinyl, and N-valproyl-4-aminobenzoyl hydrazide derivatives.
abstract: Series of Schiff bases of valproic acid hydrazide, N-valproylglycine hydrazide and N-valproyl-4-aminobenzoyl hydrazide derivatives were synthesized and characterized by IR, NMR ((1)H- and (13)C-NMR) and elemental analysis. The prepared compounds were evaluated in transgenic zebrafish embryos (Tg: flil-1: enhanced green fluorescent protein (EGFP)) for antiangiogenic activity and in HepG2 liver carcinoma cell line for anti cancer activity. The Schiff bases of N-valproylglycine hydrazide derivatives were most potent in term of suppressing angiogenic blood vessels formation and anticancer activity at very low concentration, followed by the Schiff bases of valproic acid hydrazide derivatives which exhibited moderate activity, while the Schiff bases of N-valproyl-4-aminobenzoyl hydrazide derivatives, ethyl 4-(2-propylpentanamido)benzoate (VABE) and N-(4-(hydrazinecarbonyl)phenyl)-2-propylpentanamide (VABH) in contrast exhibited pro-angiogenic activity and weaker anticancer activity which mean that these derivatives targeted a common signaling pathway in term of affecting the blood vessels formation.
authors.affiliation: Department of Chemistry, College of Science, King Saud University.
authors.forename: Ayman
authors.initials: A
authors.lastname: El-Faham
authors.forename: Muhammad
authors.initials: M
authors.lastname: Farooq
authors.forename: Sherine Nabil
authors.initials: SN
authors.lastname: Khattab
authors.forename: Ahmed Mohamed
authors.initials: AM
authors.lastname: Elkayal
authors.forename: Mahmoud Fawzy
authors.initials: MF
authors.lastname: Ibrahim
authors.forename: Nael
authors.initials: N
authors.lastname: Abutaha
authors.forename: Mohammad Ahmad
authors.initials: MA
authors.lastname: Wadaan
authors.forename: Ezzat Awad
authors.initials: EA
authors.lastname: Hamed
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012545:Schiff Bases / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014635:Valproic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D015027:Zebrafish
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D006834:Hydrazines; D012545:Schiff Bases; D014635:Valproic Acid