Eleocarpanthraquinone, a novel anthraquinone from Rhamnidium elaeocarpum (Rhamnaceae)

• Published in: Tetrahedron letters Vol. 61; no. 45; p. 152489
• Main Authors: Kauffmann, Angélica C., Oliveira, Rhayssa G.S.P., Dourado, Thainara A., Soares, Iuri N., de Sousa, Paulo T., Ribeiro, Tereza A.N., Jacinto, Marcos J., de Souza, Gabriel L.C., Judice, Wagner A. de S., Emiliano, Marli de F.C., Vianna, Luan dos S., de Carvalho, Mário G., Silva, Virgínia C.P.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 05-11-2020
• Subjects: Anthrone-anthraquinone; Cathepsins; Inhibitory potential; Parabolic competitive inhibition; Rhamnidium elaeocarpum; Rhamnidium elaeocarpum; Cathepsins; Inhibitory potential; Anthrone-anthraquinone; Parabolic competitive inhibition
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2020.152489

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•First report of new anthrone-anthraquinone from the stem bark of Rhamnidium elaeocarpum.•Eleocarpanthraquinone (1) exhibited inhibition of the cathepsins B and L.•The most stable conformer was proposed by density functional theory.
Chemical investigation of the stem bark of Rhamnidium elaeocarpum resulted in the isolation of eleocarpanthraquinone (1), a new anthrone-anthraquinone linked through a spiroketal bridge and the known anthraquinone chrysophanol (2). The structure of (1) was determined by analysis of spectrometry and spectroscopy data, including HRESIMS, 1D, and 2D NMR experiments, and optical rotation data. Eleocarpanthraquinone (1) was able to inhibit the cysteine proteases cathepsins B and L with an inhibitory potential IC50 of 3.69 ± 0.38 µM and 1.152 ± 0.025 µM, respectively. Both enzymes showed a parabolic competitive inhibition mechanism and an α parameter with respective values of 0.00253 and 0.0514, implying a positive cooperativity pathway where the binding of the first molecule potentiates the binding of the second molecule. Conformational analysis was performed using density functional theory at the M06-2X/6-31 + G(d,p) level, indicating that the triply H-bonded conformer was the most stable.