Novel [6]-gingerol Triazole Derivatives and their Antiproliferative Potential against Tumor Cells

Abstract

Background: Effective cancer treatment is a major public health challenge. The limitations of current therapies and their adverse effects reduce the efficacy of treatment, leading to significant mortality rates worldwide. Moreover, natural product chemistry occupies a prominent role in the search for new treatment alternatives, by contributing a spectrum of chemical structures that may potentially yield new bioactive compounds. The compound [6]-gingerol (1) is the main active substance in ginger (Zingiber officinale) and several studies have shown it to produce beneficial effects, including antitumor activity. Objective: This work aims to obtain new gingerol derivatives with cytotoxic activity. Method: [6]-gingerol was isolated and its derivatives were produced using click chemistry, obtaining eight new compounds. All chemical structures were determined by means of IR, NMR and HRMS data, and cytotoxicity was evaluated in the HCT 116 (colon carcinoma) and MCF-7 (breast carcinoma) cell lines at concentrations of 5 µmol L-1 and 50 µmol L-1. Results: At 50 µmol L-1, more than 70% inhibition of cell growth was achieved with compounds 2e, 2g against HCT 116, and 2b, 2d, 2e, 2f and 2g against MCF-7. Conclusion: The obtained compounds showed only moderate cytotoxic activity. However, the products with substituents occupying the meta position in relation to the triazole ring showed increased cytotoxic properties. The brominated compound (2g) showed the strongest activity, inhibiting cell proliferation by 87%.

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

“…The cells were much more sensitive to the positive control doxorubicin (IC 50 ¼ 0.5 and 1.9 mM against HCT-116 and MCF-7 cells, respectively). 40 Another study introduced different changes in the skeleton of 6-gingerol (compounds 9-14, 17 i.e. 6-shogaol, 19, and 22-24), with the aim of understanding the structure activity relationships (SAR) concerning cytotoxicity of these compounds against MCF-7 breast cancer cells.…”

6‐Gingerol and Semisynthetic 6‐Gingerdione Counteract Oxidative Stress Induced by ROS in Zebrafish

“…Compounds 1 , 2 , 3 , 5 , 7 , and 8 were tested for free radical scavenging activity using the ABTS radical cation decolorization assay with minor modifications [10] . The assay was performed by dissolving the ABTS (7 mM) in potassium persulfate (2.45 mM).…”

“…DPPH was used to determine the free radical scavenging activity of the compounds using the spectrophotometric method with slight modification. [9] Series of pure compounds 1, 2, 3, 5, 7 and 8 from the solution of different concentrations (10,20,30,40,50, and 60 μM) were prepared by diluting with ethanol. 50 μL of the sample were added to each well containing 150 μL of DPPH solution (300 μM).…”

“…Compounds 1, 2, 3, 5, 7, and 8 were tested for free radical scavenging activity using the ABTS radical cation decolorization assay with minor modifications. [10] The assay was performed by dissolving the ABTS (7 mM) in potassium persulfate (2.45 mM). Further, the reaction mixture was diluted using 0.2 M (pH 7.4) phosphate buffer (PBS) at 30 °C to obtain an absorbance 0.70 � 0.02 at 734 nm.…”

[6]-Gingerol-Derived Semi-Synthetic Compound SSi6 Inhibits Tumor Growth and Metastatic Dissemination in Triple-Negative Breast Cancer Xenograft Models

“…Natural compounds or their modified variants, such as semi-synthetic products, have been widely used for the treatment of various diseases, including breast cancer [17,18]. Gingerols are a group of biologically active phenolic compounds extracted from ginger's roots (Zingiber officinale Roscoe), [6]-gingerol (6G) being the most representative.…”