Evaluation of Microbial Transformation of 10-deoxoartemisinin by UPLC-ESI-Q-TOF-MSE

被引:8
作者
Bai, Yue [1 ,2 ]
Zhang, Dong [1 ,2 ]
Sun, Peng [1 ,2 ]
Zhao, Yifan [1 ,2 ]
Chang, Xiaoqiang [1 ,2 ]
Ma, Yue [1 ,2 ]
Yang, Lan [1 ,2 ]
机构
[1] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China
[2] China Acad Chinese Med Sci, Artemisinin Res Ctr, Beijing 100700, Peoples R China
基金
中国国家自然科学基金;
关键词
10-deoxoartemisinin; microbial transformation; hydroxylation ability; UPLC-ESI-Q-TOF-MSE; CUNNINGHAMELLA-ECHINULATA; ARTEMISININ; ANTIMALARIAL; HYDROXYLATION; DEOXOARTEMISININ; METABOLISM; BIOTRANSFORMATION;
D O I
10.3390/molecules24213874
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
10-deoxoartemisinin is a semisynthetic derivative of artemisinin that lacks a lactone carbonyl group at the 10-position, and has stronger antimalarial properties than artemisinin. However, 10-deoxoartemisinin has limited utility as a therapeutic agent because of its low solubility and bioavailability. Hydroxylated 10-deoxoartemisinins are a series of properties-improved derivatives. Via microbial transformation, which can hydroxylate 10-deoxoartemisinin at multiple sites, the biotransformation products of 10-deoxoartemisinin have been investigated in this paper. Using ultra-performance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MSE) combined with UNIFI software, products of microbial transformation of 10-deoxoartemisinin were rapidly and directly analyzed. The hydroxylation abilities of nine microorganisms were compared using this method. All of the microorganisms evaluated were able to hydroxylate 10-deoxoartemisinin, and a total of 35 hydroxylated products were identified. These can be grouped into dihydroxylated 10-deoxoartemisinins, monohydroxylated 10-deoxoartemisinins, hydroxylated dehydrogenated 10-deoxoartemisinins, and hydroxylated hydrogenated 10-deoxoartemisinins. Cunninghamella echinulata and Cunninghamella blakesleeana are able to hydroxylate 10-deoxoartemisinin, and their biotransformation products are investigated here for the first time. Cunninghamella elegans CICC 40250 was shown to most efficiently hydroxylate 10-deoxoartemisinin, and could serve as a model organism for microbial transformation. This method could be used to generate additional hydroxylated 10-deoxoartemisinins for further research.
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页数:11
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