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

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.

UPLC‐PDA coupled HR‐TOF ESI/MS2‐based identification of derivatives produced by whole‐cell biotransformation of epothilone A using Nocardia sp. CS692 and a cytochrome P450 overexpressing strain

“…24,25 Among various modifications, hydroxylation is one of the main routes of primary modifications of compounds. [26][27][28] Some of the microorganisms such as fungi Cunninghamella, Aspergillus, and Mucor succeeded in regiospecific modifications of molecules by hydroxylation in an ecofriendly environment. [29][30][31] Engineered cells such as yeasts, actinomycetes, and Escherichia coli have been used for the biotransformation of diverse metabolites.…”

“…The endogenous enzymes of cells modify the exogenously supplemented metabolites to generate chemically diverse compounds 24,25 . Among various modifications, hydroxylation is one of the main routes of primary modifications of compounds 26–28 . Some of the microorganisms such as fungi Cunninghamella, Aspergillus , and Mucor succeeded in regiospecific modifications of molecules by hydroxylation in an ecofriendly environment 29–31 .…”

Oral Bioavailability Comparison of Artemisinin, Deoxyartemisinin, and 10-Deoxoartemisinin Based on Computer Simulations and Pharmacokinetics in Rats

“…10-Deoxoartemisinin remained the peroxide bridge structure and showed an excellent antimalaria effect. There have been many novel 10-deoxoartemisinin structures designed for bioactive experiments in recent years, , implicating that it might become a hopeful candidate drug.…”

A Novel Antimalarial Metabolite in Erythrocyte From the Hydroxylation of Dihydroartemisinin by Cunninghamella elegans

“…Indeed, the exploration of active metabolites in erythrocyte is of considerable important for antimalarial drug because red blood cells are the actual sites where the plasmodium lives and the drug works. Followed by Prof. Tu, our team has been engaged in the metabolism study of ART, DHA, and its derivatives in the last few years ( Tu, 2011 ; Yang and Zhang, 2017 ; Ma et al, 2019a ; Ma et al, 2019b ; Bai et al, 2019 ; Zhao et al, 2021 ).…”