IJMS, Vol. 25, Pages 6724: Discovery of Di(het)arylmethane and Dibenzoxanthene Derivatives as Potential Anticancer Agents

IJMS, Vol. 25, Pages 6724: Discovery of Di(het)arylmethane and Dibenzoxanthene Derivatives as Potential Anticancer Agents

International Journal of Molecular Sciences doi: 10.3390/ijms25126724

Authors: Andrey Smolobochkin Dinara Niyazova Almir Gazizov Marat Syzdykbayev Alexandra Voloshina Syumbelya Amerhanova Anna Lyubina Margarita Neganova Yulia Aleksandrova Olga Babaeva Julia Voronina Nurbol Appazov Oleg Sinyashin Igor Alabugin Alexander Burilov Michail Pudovik

A family of bifunctional dihetarylmethanes and dibenzoxanthenes is assembled via a reaction of acetals containing a 2-chloroacetamide moiety with phenols and related oxygen-containing heterocycles. These compounds demonstrated selective antitumor activity associated with the induction of cell apoptosis and inhibition of the process of glycolysis. In particular, bis(heteroaryl)methane containing two 4-hydroxy-6-methyl-2H-pyran-2-one moieties combine excellent in vitro antitumor efficacy with an IC50 of 1.7 µM in HuTu-80 human duodenal adenocarcinoma models with a high selectivity index of 73. Overall, this work highlights the therapeutic potential of dimeric compounds assembled from functionalized acetals and builds a starting point for the development of a new family of anticancer agents.