Experimental and computational evaluation of dinaphthodiospyrol F and dinaphthodiospyrol G from <i>Diospyros lotus</i> L. as ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) inhibitors

By hydrolysing 2',3'-cyclic GMP-AMP dinucleotide (2',3'-cGAMP), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) regulates downstream pathways related to cancer progression and immunomodulation. Thus, it represents an attractive target for the discovery of novel ligands. We here disclose the activity of Dinaphthodiospyrol F and dinaphthodiospyrol G, two dimeric naphthoquinones extracted from <i>Diospyros lotus</i> L. as ENPP1 inhibitors by means of computational and <i>in vitro</i> techniques. Our study showed that the two molecules inhibit ENPP1 with a potency similar to that of the positive control (disodium EDTA), suggesting their possible use as new natural scaffolds in the development of optimised derivatives.