Homobutein

Oncology Reports, 15 Jun 2012, 28(3):797-805.

Natural chalcones as dual inhibitors of HDACs and NF-κB.[Reference: WebLink]

Histone deacetylase enzymes (HDACs) are emerging as a promising biological target for cancer and inflammation.
METHODS AND RESULTS:
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.
CONCLUSIONS:
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.

European Food Research & Technology, 2016, 242(1):71-90.

Antioxidant and antimalarial properties of butein and homobutein based on their ability to chelate iron (II and III) cations: a DFT study in vacuo and in solution[Reference: WebLink]

A theoretical study on the antioxidant and antimalarial properties of butein and Homobutein has been performed by considering their Fe2+ and Fe3+ chelation ability. In order to elucidate the origin of the antioxidant and antimalarial properties of these compounds, the study attempts to investigate the nature of the complex structures, ligand···Fen+ stabilities and electronic properties of the Fe cations before and after complexation.
METHODS AND RESULTS:
The investigation considered the neutral and the deprotonated species of butein and Homobutein interacting with the Fe cations as well as the deprotonated species of butein and Homobutein interacting with micro-solvated Fe2+ or Fe3+ cation. The study has been performed using B3LYP/6-31+G(d,p) method. The LANL2DZ pseudo-potential was selected to describe the Fe cations. Final energies were obtained using the B3LYP/6-311+G(2d,p)//B3LYP/6-31+G(d,p) method. The binding energies depend on the media (it is higher in vacuo than in water solution), the nature of the cation (it is higher for Fe3+ than for Fe2+), the nature of the ligand and the Fen+ coordination site on the ligand (it is highest for the bidentate Fe coordination to O2′ and O9 atoms and lowest for the Fe coordination on the π system of the aromatic ring). The charge on Fen+ decreases on coordination to the ligand.
CONCLUSIONS:
AIM analysis suggests that the strong cation···ligand interactions are more likely covalent than ionic in vacuo and entirely ionic in solution. The ability of the ligands to reduce the Fe cation coupled with the strong iron-binding properties has significant implication on their antioxidant and antimalarial activities.