title: Docking Studies of Glutamine Valproic Acid Derivative (S)-5- amino-2-(heptan-4-ylamino)-5-oxopentanoic Acid (Gln-VPA) on HDAC8 with Biological Evaluation in HeLa Cells.
abstract: In this contribution, we focused on evaluating a novel compound developed by our group. This molecule, derived from glutamine (Gln) and valproic acid (VPA), denominated (S)- 5-amino-2-(heptan-4-ylamino)-5-oxopentanoic acid (Gln-VPA), was submitted to docking studies on histone deacetylase 8 (HDAC8) to explore its non-bonded interactions. The theoretical results were validated in HeLa cells as a cancer cell model and in human dermal fibroblasts as a normal cell model. The effects of Gln-VPA on HeLa and normal fibroblasts in terms of cell survival and the ability to inhibit HDAC activity in nude nuclear proteins and in nuclear proteins of whole cells treated for 24 h were analyzed. The HeLa cell cycle was analyzed after 24 and 48 h of treatment with Gln-VPA. The docking studies show that Gln-VPA can reach the catalytic site of HDAC8. Gln-VPA was organically synthesized with a purity greater than 97%, and its structure was validated using mass spectrometry, nuclear magnetic resonance and infrared spectroscopy. Gln-VPA showed a similar effect to VPA as an HDAC inhibitor but with less toxicity to fibroblasts. Although Gln-VPA was less efficient than VPA in reducing the survival of HeLa cells, it could be studied for use as a cancer cell sensitizer.
authors: F
authors: F
authors: Martínez-Ramos
authors: G R
authors: GR
authors: Luna-Palencia
authors: I
authors: I
authors: Vásquez-Moctezuma
authors: D
authors: D
authors: Méndez-Luna
authors: M J
authors: MJ
authors: Fragoso-Vázquez
authors: J
authors: J
authors: Trujillo-Ferrara
authors: M A
authors: MA
authors: Meraz-Ríos
authors: J E
authors: JE
authors: Mendieta-Wejebe
authors: Laboratorio de Bioquímica, Laboratorio de Modelado Molecular, Bioinformática y Diseño de Fármacos de la Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Casco de Santo Tomás, Distrito Federal, 11340, México.
authors: J
authors: J
authors: Correa-Basurto
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000187:drug effects; D005973:Glutamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014635:Valproic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C000620177:5-amino-2-(heptan-4-ylamino)-5-oxopentanoic acid; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D012097:Repressor Proteins; D005973:Glutamine; D014635:Valproic Acid; C409470:HDAC8 protein, human; D006655:Histone Deacetylases