Bergenin of Peltophorum dubium (Fabaceae) Roots and Its Bioactive Semi‑Synthetic Derivatives

Oscar Da Silva Neto,Bruna Do Nascimento,Juceni David,Jorge David,Eliane Silva,Klauber Cardoso,Marla Teodoro

doi:10.21577/0103-5053.20200141

Oscar Da Silva Neto, Bruna Do Nascimento + Show 5 more

Open Access

https://doi.org/10.21577/0103-5053.20200141

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Abstract

This work describes the isolation of pure bergenin from Peltophorum dubium roots with good yields and its further derivatization through Williamson synthesis. The alkyl derivatives of the bergenin were identified by nuclear magnetic resonance and mass spectrometry data analysis. Among them, three derivatives were reported for the first time herein, 8,10-dihexyl-bergenin, 8,10-didecyl-bergenin, and 8,10-ditetradecyl-bergenin, along with three previously reported ones (8,10-dimethylbergenin, 8-methylbergenin, 8,10-dioctyl-bergenin). Most derivatives of the bergenin displayed moderate cytotoxicity against Artemia salina, except the 8,10-dihexyl-bergenin (lethal concentration doses for 50% (LC50) = 70.55 µg mL-1). The antimicrobial assay showed that all derivatives selectively inhibited the Gram-positive bacteria Staphylococcus aureus, and two of them (8,10-dihexyl-bergenin and 8,10-didecyl-bergenin) had promising activities (minimum inhibitory concentration (MIC) = 5.1-6.2 µmol L-1). In addition, bergenin displayed interesting inhibition on acetylcholinesterase (half maximal inhibitory concentration (IC50) = 141.19 ± 0.41 µmol L-1), while its semi-synthetic derivatives displayed modest activity. Our results revealed that the antibacterial activity of bergenin could be greatly improved through its structural modification.

Highlights

Nature is an extremely rich source of highly diverse and innovative chemical structures
As part of our ongoing investigations on bioactivities of derivatives of natural products, this study describes a simple procedure for the isolation of bergenin (1) in good yields from roots of P. dubium
The proposed method for extraction and purification of the bergenin (1) from the methanolic extract of P. dubium roots furnished the pure compound in good yield (7.67 × 10‐2% of dry roots and 3.19% of extract)

Summary

Introduction

Nature is an extremely rich source of highly diverse and innovative chemical structures. 8,10-Dihexyl-bergenin (3) Amorphous white solid, yield 89%; 1H NMR (500 MHz, CD3OD) d 0.95 (6H, t), 1.30-1.60 (16H, m), 1.75-1.90 (4H, m), 3.90 (3H, s), 4.82 (1H, d, J 10.3 Hz), 7.45 (1H, s); LR-ESIMS m/z, C26H40O9 [M + Na]+: 519.32, [2M + Na]+: 1015.55. 8,10-Dioctyl-bergenin (4) Amorphous white solid, yield of 92%; 1H NMR (300 MHz, CDCl3) d 0.90 (6H, t), 1.25-1.65 (24H, m), 1.75-1.85 (4H, m), 3.91 (3H, s), 4.74 (1H, d, J 10.2 Hz), 7.40 (1H, s); LR-ESIMS m/z, C30H48O9 [M + Na]+: 575.38, [2M + Na]+: 1127.70. 8,10-Didecyl-bergenin (5) Amorphous white solid, yield of 76%; 1H NMR (300 MHz, CD3OD) d 0.90 (6H, t), 1.30-1.60 (32H, m), 1.80 (4H, m), 3.92 (3H, s), 4.82 (1H, d, J 10.2 Hz), 7.45 (1H, s); LR-ESIMS m/z, C34H56O9 [M + Na]+: 631.46, [2M + Na]+: 1239.81. The lethal concentration doses for 50% of the brine shrimp (LC50) and the respective 95% confidence intervals were determined by using the GraphPad Prism (La Jolla, CA) software.[18]

Evaluation of antibacterial activity

Results and Discussion

Conclusions