Synthesis of Oleanolic Acid-Dithiocarbamate Conjugates and Evaluation of Their Broad-Spectrum Antitumor Activities.

Efficient and mild synthetic routes for bioactive natural product derivatives are of current interest for drug discovery. Herein, on the basis of the pharmacophore hybrid strategy, we report a two-step protocol to obtain a series of structurally novel oleanolic acid (OA)-dithiocarbamate conjugates in mild conditions with high yields. Moreover, biological evaluations indicated that representative compound exhibited the most potent and broad-spectrum antiproliferative effects against Panc1, A549, Hep3B, Huh-7, HT-29, and Hela cells with low cytotoxicity on normal cells.

PROTACs in gastrointestinal cancers.

Proteolysis targeting chimera (PROTAC) presents a powerful strategy for targeted protein degradation (TPD). The heterobifunctional PROTAC molecule consists of an E3 ligase ligand covalently linked to a protein of interest (POI) via a linker. PROTAC can induce ubiquitinated proteasomal degradation of proteins by hijacking the ubiquitin-proteasome degradation system (UPS).

Carboranes as unique pharmacophores in antitumor medicinal chemistry.

Carborane is a carbon-boron molecular cluster that can be viewed as a 3D analog of benzene. It features special physical and chemical properties, and thus has the potential to serve as a new type of pharmacophore for drug design and discovery. Based on the relative positions of two cage carbons, icosahedral -carboranes can be classified into three isomers, -carborane (-carborane, 1,2-CBH), -carborane (-carborane, 1,7-CBH), and -carborane (-carborane, 1,12-CBH), and all of them can be deboronated to generate their - forms.