Synthesis, X-ray crystal structure, DFT calculation and anti-tumor research of novel-configurational dihydroartemisinin purine hybrids

Abstract

The diastereomers 10-N-[2-fluoro-6-chloro-9H-9-purinyl]-(9R, 10R)-dihydroartemisinin(A) and10-N-[2-fluoro-6-chloro-9H-9-purinyl]-(9S, 10S)-dihydroartemisinin(B) were obtained via a trifluoroacetic acid catalyzed procedure simultaneously. Their structures were characterized by HRMS, MS, ¹H-NMR, ¹³C-NMR, 2D NMR(COSY) and IR spectroscopy, and the configurations were further confirmed by X-Ray diffraction and Density functional theory (DFT). Then, the intermolecular interactions were studied mainly through Hershfield surface (HS), molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) methods. Finally, preliminary anticancer evaluations of A and B were conducted in human breast tumor cell lines (MDA-MB-436, T47D) and a normal mammary epithelial cell line (MCF-10A). The GI₅₀ of A and B were better or comparable to the positive drug mercaptopurine (6-MP), and both of novel compounds did not display significant cytotoxicity toward MCF-10A.

Keywords:

• anti-tumor
• DFT calculation
• dihydroartemisinin (DHA) purine hybrids
• X-ray diffraction

Acknowledgements

This research was supported by Guizhou Provincial Natural Science Foundation ([2019]1121) and the Fostering Projects of Guizhou University ([2020]83). Theoretical calculations were performed at the ScGrid and Deepcomp7000 Supercomputing Center of the Network Information Center of the Chinese Academy of Sciences.

Disclosure statement

No potential conflict of interest was reported by the authors.