Molecular Crystals and Liquid Crystals ( IF 0.7 ) Pub Date : 2022-08-19 , DOI: 10.1080/15421406.2022.2111882 Bing-Qing Li 1, 2 , Jie Ding 1, 2 , Chang-Guang Zeng 3 , Yu-Yang Song 1, 2 , Kai Xia 1, 2 , Yi Ai 1, 2 , Jun-Jie Zhu 1, 2 , Hang Zhong 1, 2 , Zhi-Xu Zhou 1, 2
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.
中文翻译:
新型构型双氢青蒿素嘌呤杂合物的合成、X射线晶体结构、DFT计算及抗肿瘤研究
摘要
非对映异构体10- N- [2-fluoro-6-chloro-9H-9 - purinyl]-(9R,10R)-dihydroartemisinin( A )和10- N- [2-fluoro-6-chloro-9H - 9 -嘌呤基]-(9S,10S)-二氢青蒿素( B )同时通过三氟乙酸催化得到。它们的结构通过 HRMS、MS、1 H-NMR、13C-NMR,2D NMR(COSY)和IR光谱,以及X射线衍射和密度泛函理论(DFT)进一步证实了构型。然后,主要通过Hershfield表面(HS),分子静电势(MEP)和前沿分子轨道(FMO)方法研究分子间相互作用。最后,在人乳腺肿瘤细胞系(MDA-MB-436、T47D)和正常乳腺上皮细胞系(MCF-10A)中进行A和B的初步抗癌评估。A和B的GI 50优于或与阳性药物巯基嘌呤 (6-MP) 相当,并且两种新化合物均未显示出对 MCF-10A 的显着细胞毒性。