Synthesis, crystal structure, DFT and anticancer study of dihydroartermisinin-paracetamol hybrids

Abstract

A pair of C-10 epimers of dihydroartermisinin-paracetamol hybrids (A and B) were prepared in this work, and both of which were characterized by MS, 1H NMR, 13C NMR, IR and ECD spectra as well as by a single crystal X-ray structural analysis. Subsequently, the structures of the two compounds were analyzed with DFT-based approaches. The analytical results on conformations indicated that the DFT-optimized molecular structures were consistent with the crystal structures confirmed by X-ray diffraction. The packing of the molecules in the solid state was stabilized by hydrogen bonds. The signs of the experimental IR and ECD spectra was also efficiently simulated by the DFT methods. A primary evaluation on anticancer effects of A and B was conducted towards human breast tumor cell line MCF-7 and human colon tumor cell line HCT116, the results demonstrated that 10-α-O-(4-acetylamino) phenyl dihydroartemisinin (A) was slightly less potent than its 10-β counterpart (B) in both tested cell lines.