Biological Evaluation and Docking Studies of Synthetic Oleanane-type Triterpenoids.

Autor: Ortega-Muñoz M; Department of Organic Chemistry, Faculty of Sciences, Department of Organic Chemistry, Biotechnology Institute, Institute of Biopathology and Regenerative Medicine (IBIMER), and Department of Human Anatomy and Embryology, University of Granada, 18071 Granada, Spain.; Department of Organic Chemistry, Faculty of Sciences, Department of Organic Chemistry, Biotechnology Institute, Institute of Biopathology and Regenerative Medicine (IBIMER), and Department of Human Anatomy and Embryology, University of Granada, 18071 Granada, Spain., Rodríguez-Serrano F; Department of Organic Chemistry, Faculty of Sciences, Department of Organic Chemistry, Biotechnology Institute, Institute of Biopathology and Regenerative Medicine (IBIMER), and Department of Human Anatomy and Embryology, University of Granada, 18071 Granada, Spain.; Department of Organic Chemistry, Faculty of Sciences, Department of Organic Chemistry, Biotechnology Institute, Institute of Biopathology and Regenerative Medicine (IBIMER), and Department of Human Anatomy and Embryology, University of Granada, 18071 Granada, Spain.; Biosanitary Research Institute of Granada (ibs.GRANADA), 18071 Granada, Spain., De Los Reyes-Berbel E; Department of Organic Chemistry, Faculty of Sciences, Department of Organic Chemistry, Biotechnology Institute, Institute of Biopathology and Regenerative Medicine (IBIMER), and Department of Human Anatomy and Embryology, University of Granada, 18071 Granada, Spain., Mut-Salud N; Department of Organic Chemistry, Faculty of Sciences, Department of Organic Chemistry, Biotechnology Institute, Institute of Biopathology and Regenerative Medicine (IBIMER), and Department of Human Anatomy and Embryology, University of Granada, 18071 Granada, Spain., Hernández-Mateo F; Department of Organic Chemistry, Faculty of Sciences, Department of Organic Chemistry, Biotechnology Institute, Institute of Biopathology and Regenerative Medicine (IBIMER), and Department of Human Anatomy and Embryology, University of Granada, 18071 Granada, Spain.; Department of Organic Chemistry, Faculty of Sciences, Department of Organic Chemistry, Biotechnology Institute, Institute of Biopathology and Regenerative Medicine (IBIMER), and Department of Human Anatomy and Embryology, University of Granada, 18071 Granada, Spain., Rodríguez-López A; Department of Organic Chemistry, Faculty of Sciences, Department of Organic Chemistry, Biotechnology Institute, Institute of Biopathology and Regenerative Medicine (IBIMER), and Department of Human Anatomy and Embryology, University of Granada, 18071 Granada, Spain., Garrido JM; Department of Organic Chemistry, Faculty of Sciences, Department of Organic Chemistry, Biotechnology Institute, Institute of Biopathology and Regenerative Medicine (IBIMER), and Department of Human Anatomy and Embryology, University of Granada, 18071 Granada, Spain.; Biosanitary Research Institute of Granada (ibs.GRANADA), 18071 Granada, Spain.; Department of Cardiovascular Surgery, Virgen de las Nieves University Hospital, 18071 Granada, Spain., López-Jaramillo FJ; Department of Organic Chemistry, Faculty of Sciences, Department of Organic Chemistry, Biotechnology Institute, Institute of Biopathology and Regenerative Medicine (IBIMER), and Department of Human Anatomy and Embryology, University of Granada, 18071 Granada, Spain.; Department of Organic Chemistry, Faculty of Sciences, Department of Organic Chemistry, Biotechnology Institute, Institute of Biopathology and Regenerative Medicine (IBIMER), and Department of Human Anatomy and Embryology, University of Granada, 18071 Granada, Spain., Santoyo-González F; Department of Organic Chemistry, Faculty of Sciences, Department of Organic Chemistry, Biotechnology Institute, Institute of Biopathology and Regenerative Medicine (IBIMER), and Department of Human Anatomy and Embryology, University of Granada, 18071 Granada, Spain.; Department of Organic Chemistry, Faculty of Sciences, Department of Organic Chemistry, Biotechnology Institute, Institute of Biopathology and Regenerative Medicine (IBIMER), and Department of Human Anatomy and Embryology, University of Granada, 18071 Granada, Spain.
Jazyk: angličtina
Zdroj: ACS omega [ACS Omega] 2018 Sep 30; Vol. 3 (9), pp. 11455-11468. Date of Electronic Publication: 2018 Sep 20.
DOI: 10.1021/acsomega.8b01034
Abstrakt: Saponins are potential wide-spectrum antitumor drugs, and copper(I) catalyzed azide-alkyne 1,3-dipolar cycloaddition is a suitable approach to synthesizing saponin-like compounds by regioselective glycosylation of the C2/C3 hydroxyl and C28 carboxylic groups of triterpene aglycones maslinic acid (MA) and oleanolic acid (OA). Biological studies on the T-84 human colon carcinoma cell line support the role of the hydroxyl groups at C2/C3, the influence of the aglycone, and the bulky nature of the substituents in C28. OA bearing a α-d-mannose moiety at C28 (compound 18 ) focused our interest because the estimated inhibitory concentration 50 was similar to that reported for ginsenoside Rh2 against colon cancer cells and it inhibits the G 1 -S phase transition affecting the cell viability and apoptosis. Considering that triterpenoids from natural sources have been identified as inhibitors of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling, docking studies were conducted to evaluate whether NF-κB may be a potential target. Results are consistent with the biological study and predict a similar binding mode of MA and compound 18 to the p52 subunit from NF-κB but not for OA. The fact that the binding site is shared by the NF-κB inhibitor 6,6-dimethyl-2-(phenylimino)-6,7-dihydrobenzo[ d ][1,3]oxathiol-4(5 H )-one supports the result and points to NF-κB as a potential target of both MA and compound 18 .
Competing Interests: The authors declare no competing financial interest.
Databáze: MEDLINE
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