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

Yue Bai,Dong Zhang,Yifan Zhao,Yue Ma,Lan Yang,Xiaoqiang Chang,Peng Sun

doi:10.3390/molecules24213874

Abstract

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.

Highlights

Artemisinin is a first-line antimalarial agent, which is first derived from Chinese herb by ProfessorTu [1]. 10-deoxoartemisinin is a bioactive derivative of artemisinin, first prepared by the simple transformation in 1990 [2]
Microbial transformation is an an increasingly increasingly popular popular method method used used to to modify modify small small molecules, molecules, Microbial transformation is adept at generating hydroxylated derivatives, because many enzymes adept at generating hydroxylated derivatives, because many enzymes catalyze catalyze hydroxylation reactions, reactions, and
CGMCC 3.5771, C. echinulata 3.4879, and C. elegans CGMCC 3.4832 were obtained from the China

Summary

Introduction

Artemisinin is a first-line antimalarial agent, which is first derived from Chinese herb by ProfessorTu [1]. 10-deoxoartemisinin is a bioactive derivative of artemisinin, first prepared by the simple transformation in 1990 [2]. Artemisinin is a first-line antimalarial agent, which is first derived from Chinese herb by Professor. 10-deoxoartemisinin is a bioactive derivative of artemisinin, first prepared by the simple transformation in 1990 [2]. It lacks the C-10 lactone carbonyl group of artemisinin, but retains its antimalarial endoperoxide activity [3]. The derivate was eight times more active against multidrug-resistant malaria in vitro [2]. Poor solubility and bioavailability are the barriers for further application in the clinic. 10-deoxoartemisinin has impressive antitumor and antiangiogenesis activities [4,5,6]. As a part of our ongoing projects [7,8,9,10], novel

Methods

Discussion

Conclusion