Synthesis, X-ray crystal structure, DFT calculation and anti-tumor research of novel-configurational dihydroartemisinin purine hybrids. Issue 1 (3rd May 2023)

• Record Type: Journal Article
• Authors: Li, Bing-Qing; Ding, Jie; Zeng, Chang-Guang; Song, Yu-Yang; Xia, Kai; Ai, Yi; Zhu, Jun-Jie; Zhong, Hang; Zhou, Zhi-Xu
• Is Part Of: Molecular crystals and liquid crystals. Volume 756:Issue 1(2023)
• Page Start: 58
• Page End: 73
• Publication Date: 2023-05-03
• Subjects: anti-tumor -- DFT calculation -- dihydroartemisinin (DHA) purine hybrids -- X-ray diffraction; Molecular crystals -- Periodicals; Liquid crystals -- Periodicals; Liquid crystals; Molecular crystals; Periodicals; 548
• DOI: 10.1080/15421406.2022.2111882
• Languages: English
• ISSNs: 1542-1406

Abstract

Abstract: The diastereomers 10- N -[2-fluoro-6-chloro-9 H -9-purinyl]-(9R, 10R)-dihydroartemisinin(A ) and10- N -[2-fluoro-6-chloro-9 H -9-purinyl]-(9S, 10S)-dihydroartemisinin(B ) were obtained via a trifluoroacetic acid catalyzed procedure simultaneously. Their structures were characterized by HRMS, MS, 1 H-NMR, 13 C-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.