Chalcones are absorbed in the daily diet and appear to be promising cancer chemopreventive agents. Chalcones represent an important group of the polyphenolic family, which includes a large number of naturally occurring molecules. This family possesses an interesting spectrum of biological activities, including antioxidative, antibacterial, anti-inflammatory, anticancer, cytotoxic, and immunosuppressive potential. Compounds of this family have been shown to interfere with each step of carcinogenesis, including initiation, promotion and progression. Moreover, numerous compounds from the family of dietary chalcones appear to show activity against cancer cells, suggesting that these molecules or their derivatives may be considered as potential anticancer drugs. This review will focus primarily on prominent members of the chalcone family with an 1,3-diphenyl-2-propenon core structure. Specifically, the inhibitory effects of these compounds on the different steps of carcinogenesis that reveal interesting chemopreventive and chemotherapeutic potential will be discussed.

Over the centuries, plant extracts have been used to treat various diseases. Until now, natural products have played an important role in anticancer therapy as there are more than 500 compounds from terrestrial and marine plants or microorganisms, which have antioxidant, antiproliferative, or antiangiogenic properties and are therefore able to reduce tumor growth. The recent discovery of new natural products has been accelerated by novel technologies (high throughput screening of natural products in plants, animals, marine organisms, and microorganisms). Vincristine, irinotecan, etoposide, and paclitaxel are examples of compounds derived from plants that are used in cancer treatment. Similarly, actinomycin D, mitomycin C, bleomycin, doxorubicin, and L-asparaginase are drugs derived from microorganisms. In this review, we describe the molecular mechanisms of natural compounds with anti-inflammatory and anticancer activities.

No abstract

Two new metabolites, embellicines A and B (1 and 2), were isolated from the EtOAc extract of the fungus Embellisia eureka , an endophyte of the Moroccan plant Cladanthus arabicus (Asteraceae). The structures of these new compounds were determined on the basis of extensive one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. The absolute configuration of embellicine A (1) was determined by TDDFT ECD calculations of solution conformers, whereas that of embellicine B (2) was deduced based on ROESY correlations and on biogenetic considerations in comparison to 1. Both embellicines (1 and 2) are cytostatic, cytotoxic, and inhibit NF-κB transcriptional activity, indicating that inhibition of NF-κB may be a possible mechanism of action of these compounds. Embellicine B (2) was the most active compound encountered in this study and acts at nanomolar concentrations without affecting tumor microenvironment.

Histone deacetylase enzymes (HDACs) are emerging as a promising biological target for cancer and inflammation. Using a fluorescence assay, we tested the in vitro HDAC inhibitory activity of twenty-one natural chalcones, a widespread group of natural products with well-known anti-inflammatory and antitumor effects. Since HDACs regulate the expression of the transcription factor NF-κB, we also evaluated the inhibitory potential of the compounds on NF-κB activation. Only four chalcones, isoliquiritigenin (no. 10), butein (no. 12), homobutein (no. 15) and the glycoside marein (no. 21) showed HDAC inhibitory activity with IC50 values of 60–190 μM, whereas a number of compounds inhibited TNFα-induced NF-κB activation with IC50 values in the range of 8–41 μM. Interestingly, three chalcones (nos. 10, 12 and 15) inhibited both TNFα-induced NF-κB activity and total HDAC activity of classes I, II and IV. Molecular modeling and docking studies were performed to shed light into dual activity and to draw structure-activity relationships among chalcones (nos. 1–21). To the best of our knowledge this is the first study that provides evidence for HDACs as potential drug targets for natural chalcones. The dual inhibitory potential of the selected chalcones on NF-κB and HDACs was investigated for the first time. This study demonstrates that chalcones can serve as lead compounds in the development of dual inhibitors against both targets in the treatment of inflammation and cancer.