Synthesis and DNA interaction of aloe-emodin α-amino phosphate derivatives

•Aloe-emodin α-amino phosphate derivatives with targeting DNA were synthesized.•The introduction of phosphoramidate can increase lipophilicity the compounds and promote them to enter the nucleus.•The main interaction mode of Aloe-emodin α-amino phosphate derivatives with DNA is intercalation.•Aloe-emodin α-amino phosphate derivatives could increase the DNA fragmentation of cancer cells and possessed strong anti-tumor potential. Square-planar aromatic compounds (such as aloe emodin) have been widely studied for their anti-tumor potential. However, It still suffer from poor cells membrane permeability and low bioavailability. To solve this problem, we introduced α-amino phosphate on the anthraquinone scaffold to increasing the permeability of the cancer cells. 13 aloe emodin α-amino phosphate derivatives were synthesized. Among them, compounds 2a and 2b showed better anti-tumor activity than aloe-emodin in different tumor cells. The interaction between compounds 2a, 2b and calf thymus DNA (Ct-DNA) was studied via UV–vis absorption, fluorescence spectrum, viscosity measurements and molecular docking. The results show that the interaction mode of 2a and 2b with DNA is intercalation. Under confocal microscopy, 2a and 2b can effectively penetrate the cell membrane, nuclear membrane and enter the nucleus. Comet assay showed that compound 2b could increase the DNA fragmentation of cancer cells .Contain α-amino-phosphate anthraquinone scaffold emerges as a promising anticancer activity structure and our results may provide a structural modification direction for improving the membrane permeability of anthraquinones and other drugs. Aloe-emodin α-amino phosphate derivatives were synthesized. It is worth noting that the compounds 2a and 2b can enter the nuclear membrane and bind to DNA by intercalating mode to inhibit the proliferation of tumor cells. [Display omitted]