Proteasome as a New Target for Bio‐Inspired Benzo[k,l]xanthene Lignans

Abstract

Mass spectrometry-based chemical proteomics is a powerful tool for the target discovery of small molecules. Here, the application of this approach is presented to define the target profile of bio-inspired synthetic benzo[k,l]xanthene lignans endowed with interesting biological properties. Proteasome has been identified as a new main interactor for this class of compounds. A combination of molecular docking with in vitro and in cell fluorescence assays gave insights on the molecular mechanism of the interaction, highlighting the tendency of these lignans to inhibit the proteasome.

Synthesis of Bisphenol Neolignans Inspired by Honokiol as Antiproliferative Agents

“…Thus, in continuation of our previous studies on the synthesis of natural-derived polyphenols with antitumor [27][28][29][30][31], antioxidant, hypoglycemic [32,33], antifungal [34], and anti-inflammatory activity [35,36], we oriented our recent works toward the synthesis of magnolol analogues, which were evaluated as potential antidiabetic [26], anticancer [37], and antioxidative [38] agents. As a further contribution, in the present work we report the synthesis of bisphenols neolignans inspired by honokiol (2).…”

Characterization and Interaction with Biomembrane Model of Benzo[k,l]xanthene Lignan Loaded Solid Lipid Nanoparticles

“…In 2009, a simple and biomimetic methodology for the synthesis of BXLs was published [7], and a variety of synthetic benzoxanthenes have since been obtained and evaluated as antioxidant [8], anti-inflammatory [9], selective copper-chelators [10], antifungal [11], antibacterial [12], antiproliferative agents [13,14]. Additionally, BXLs are reported to induce autophagy towards tumor cells [15] and act as antiangiogenic [16], pro-apoptotic agents [17], DNA-binders [12,17], proteasome inhibitors [18], all targets involved in tumorigenesis, and which are useful for the development of anticancer drugs. These studies highlighted the promising biological activities of this class of lignans as potential chemotherapeutic agents.…”

A Rare Natural Benzo[k,l]xanthene as a Turn-Off Fluorescent Sensor for Cu2+ Ion

“…Because of the rarity of benzoxanthene lignans, their biological properties and possible applications are almost unexplored if we exclude some works in which these compounds have been proven as antifungal agents [ 19 ], anti-inflammatory agents [ 20 ], and useful antiproliferative compounds against different tumor cell lines, with antioxidant and antiangiogenic activities [ 17 , 21 , 22 , 23 ]. Some of these compounds were also subjected to STD-NMR measurements and molecular docking calculations; the obtained data indicate that benzoxanthene lignans interact with the DNA in two ways: the planar core intercalates between two base pairs in the DNA while the ester groups, which behave as flexible pendants, bind to the minor groove of the nucleic acid [ 17 ].…”