Medicinal chemistry inspired by ginger: exploring the chemical space around 6-gingerol

Abstract

Ginger (Zingiber officinale Roscoe) has been used as a spice and as a traditional remedy since ancient times, especially in traditional Chinese medicine. It has been applied as a treatment for many diseases either alone or in combination with other remedies. Many studies were conducted on ginger and its constituents and a wide array of bioactivities were reported, e.g., antioxidant, anti-inflammatory, antiemetic, and anticancer activity. Most of these had been correlated to gingerols and shogaols, the most abundant secondary metabolites in ginger. This inspired several research groups to explore the biomedical value of the chemical space around these compounds, and many of their synthetic or semi-synthetic analogues have been prepared and studied for various bioactivities. Thanks to this, many valuable structure activity relationships have been revealed for such compounds. Herein, we provide a brief summary on the synthetic derivatization efforts that had so far been implemented on 6-gingerol, the main constituent of fresh ginger. This review covers 160 natural, semisynthetic, or synthetic 6-gingerol derivatives and their reported bioactivities.

Fig. 1. The structure of 6-gingerol, i.e. 5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)decan-3-one.

Fig. 2. Semi-synthetic gingerol derivatives prepared and directly or indirectly evaluated for their in vitro antitumor potential.

Fig. 3. Semi-synthetic gingerol derivatives prepared and evaluated for their in vitro anti-inflammatory activity.

Fig. 4. Semi-synthetic gingerol derivatives prepared and evaluated for their in vitro antibacterial activity.

Fig. 5. Semi-synthetic gingerol derivatives prepared and evaluated for their in vitro anti-platelet activity.

Fig. 6. Semi-synthetic gingerol derivatives with miscellaneous bioactivities. Compounds are presented that were prepared and evaluated for their effect on the intracellular Ca²⁺ homeostasis, TRPV1 and TRPA1 ion channels, or as potential antidiabetic or hepatoprotective agents.