Inverse Virtual Screening for the rapid re-evaluation of the presumed biological safe profile of natural products. The case of steviol from Stevia rebaudiana glycosides on farnesoid X receptor (FXR)

被引：3

作者：

Potenza, Marianna ^{[1
]}

Cavalluzzi, Maria Maddalena ^{[2
]}

Milani, Gualtiero ^{[2
]}

Lauro, Gianluigi ^{[1
]}

Carino, Adriana ^{[3
]}

Roselli, Rosalinda ^{[4
]}

Fiorucci, Stefano ^{[3
]}

Zampella, Angela ^{[4
]}

Pierri, Ciro Leonardo ^{[5
]}

Lentini, Giovanni ^{[2
]}

Bifulco, Giuseppe ^{[1
]}

机构：

[1] Univ Salerno, Dept Pharm, Via Giovanni Paolo II 132, I-84084 Fisciano, Italy

[2] Univ Bari Aldo Moro, Dept Pharm Drug Sci, Via Edoardo Orabona 4, I-70126 Bari, Italy

[3] Nuova Fac Med, Dept Surg & Biomed Sci, Perugia, Italy

[4] Univ Naples Federico II, Dept Pharm, Via Domenico Montesano 49, I-80131 Naples, Italy

[5] Univ Bari Aldo Moro, Dept Biosci Biotechnol & Biopharmaceut, Via Edoardo Orabona 4, I-70126 Bari, Italy

来源：

BIOORGANIC CHEMISTRY | 2021年 / 111卷

关键词：

Inverse virtual screening; Natural products; Molecular docking; Target identification; Farnesoid X receptor; WEB SERVER; IDENTIFICATION; ANTAGONIST; DISCOVERY; BINDING; DESIGN; UPDATE; LIGAND; POTENT; POLYPHARMACOLOGY;

D O I：

10.1016/j.bioorg.2021.104897

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Nonnutritive sweeteners (NNSs) are widely employed as dietary substitutes for classical sugars thanks to their safety profile and low toxicity. In this study, a re-evaluation of the biological effects of steviol (1), the main metabolite from Stevia rebaudiana glycosides, was performed using the Inverse Virtual Screening (IVS) target fishing computational approach. Starting from well-known pharmacological properties of Stevia rebaudiana glycosides, this computational tool was employed for predicting the putative interacting targets of 1 and, afterwards, of its five synthetic ester derivatives 2-6, accounting a large panel of proteins involved in cancer and inflammation events. Applying this methodology, the farnesoid X receptor (FXR) was identified as the putative target partner of 1-6. The predicted ligand-protein interactions were corroborated by transactivation assays, specifically disclosing the agonistic activity of 1 and the antagonistic activities of 2-6 on FXR. The reported results highlight the feasibility of IVS as a fast and potent tool for predicting the interacting targets of query compounds, addressing the re-evaluation of their bioactivity. In light of the obtained results, the presumably safe profile of known compounds, such as the case of steviol (1), is critically discussed.

引用

页数：12