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Glutaminase plays an important role in carcinogenesis and cancer cell growth. This biological target is interesting against cancer cells. Therefore, in this work, in silico [docking and molecular dynamics (MD) simulations] and in vitro methods (antiproliferative and LC-MS metabolomics) were employed to assay a hybrid compound derived from glutamine and valproic acid (Gln-VPA), which was compared with 6-diazo-5-oxo-L-norleucine (DON, a glutaminase inhibitor) and VPA (contained in Gln-VPA structure). Docking results from some snapshots retrieved from MD simulations show that glutaminase recognized Gln-VPA and DON. Additionally, Gln-VPA showed antiproliferative effects in HeLa cells and inhibited glutaminase activity. Finally, the LC-MS-based metabolomics studies on HeLa cells treated with either Gln-VPA (IC 60 = 8 mM) or DON (IC 50 = 3.5 mM) show different metabolomics behaviors, suggesting that they modulate different biological targets of the cell death mechanism. In conclusion, Gln-VPA is capable of interfering with more than one pharmacological target of cancer, making it an interesting drug that can be used to avoid multitherapy of classic anticancer drugs.

Titel:	Molecular modeling and LC-MS-based metabolomics of a glutamine-valproic acid (Gln-VPA) derivative on HeLa cells.
Autor/in / Beteiligte Person:	Fragoso-Vázquez, MJ ; Méndez-Luna, D ; Rosales-Hernández, MC ; Luna-Palencia, GR ; Estrada-Pérez, A ; Fromager, B ; Vásquez-Moctezuma, I ; Correa-Basurto, J
Link:	Zum Volltext
Zeitschrift:	Molecular diversity, Jg. 25 (2021-05-01), Heft 2, S. 1077-1089
Veröffentlichung:	Leiden, The Netherlands : ESCOM Science Publishers, c1995-, 2021
Medientyp:	academicJournal
ISSN:	1573-501X (electronic)
DOI:	10.1007/s11030-020-10089-z
Schlagwort:	Cell Proliferation drug effects Cell Survival drug effects Chromatography, Liquid Glutaminase antagonists & inhibitors Glutaminase chemistry HeLa Cells Humans Mass Spectrometry Metabolome drug effects Metabolomics Models, Molecular Antineoplastic Agents chemistry Antineoplastic Agents pharmacology Glutamine chemistry Glutamine pharmacology Valproic Acid chemistry Valproic Acid pharmacology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Mol Divers] 2021 May; Vol. 25 (2), pp. 1077-1089. <i>Date of Electronic Publication: </i>2020 Apr 24. MeSH Terms: Antineoplastic Agents* / chemistry ; Antineoplastic Agents* / pharmacology ; Glutamine* / chemistry ; Glutamine* / pharmacology ; Valproic Acid* / chemistry ; Valproic Acid* / pharmacology ; Cell Proliferation / drug effects ; Cell Survival / drug effects ; Chromatography, Liquid ; Glutaminase / antagonists & inhibitors ; Glutaminase / chemistry ; HeLa Cells ; Humans ; Mass Spectrometry ; Metabolome / drug effects ; Metabolomics ; Models, Molecular References: Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674. https://doi.org/10.1016/j.cell.2011.02.013. (PMID: 10.1016/j.cell.2011.02.0132137623021376230) ; Jones RG, Thompson CB (2009) Tumor suppressors and cell metabolism: a recipe for cancer growth. 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Molecular modeling and LC-MS-based metabolomics of a glutamine-valproic acid (Gln-VPA) derivative on HeLa cells.