In vitro antimalarial studies of novel artemisinin biotransformed products and its derivatives

Gaur, Rashmi; Darokar, Mahendra P.; Ajayakumar, P. V.; Shukla, R. S.; Bhakuni, R. S.

doi:10.1016/j.phytochem.2014.08.004

Cited by 21 publications

(15 citation statements)

References 26 publications

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“…Data of 1 H and 13 C NMR spectra of product 2 were in agreement with the reported literatures’ data (Lee et al 1989; Gaur et al 2014). So product 2 was identified as 1-deoxyartemisinin (Fig.…”

Section: Resultssupporting

confidence: 91%

“…The modification of artemisinin has been studied by chemical and biological methods in some reports (Gaur et al 2014; Parshikov et al 2004, 2006; Zhan et al 2002; Goswami et al 2010; Acton 1999). However, synthesis and semisynthesis of artemisinin derivatives are impossible or impracticable because of the complexity of the artemisinin molecule and the chemical lability of the peroxy ring system.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, microbial transformation is a promising route to obtain artemisinin derivatives. There are many reports on microbial transformation of artemisinin by various microorganisms, such as Aspergillus niger , Rhizopus stolonifer , Cunninghamella elegans , Eurotium amstelodami , Mucor polymorphosporus , Penicillium simplicissimum , Streptomyces griseus (Zhan et al 2015; Gaur et al 2014; Goswami et al 2010; Liu et al 2006; Parshikov et al 2004, 2006; Zhan et al 2002). Here, we first report the microbial transformation of artemisinin by A. terreus .…”

Section: Resultsmentioning

confidence: 99%

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Microbial transformation of artemisinin by Aspergillus terreus

Zhu

Zhan

2017

Bioresour. Bioprocess.

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BackgroundArtemisinin (1) and its derivatives are now being widely used as antimalarial drugs, and they also exhibited good antitumor activities. So there has been much interest in the structural modification of artemisinin and its derivatives because of their effective bioactivities. The microbial transformation is a promising route to obtain artemisinin derivatives. The present study focuses on the microbial transformation of artemisinin by Aspergillus terreus.ResultsDuring 6 days at 28 °C and 180 rpm, Aspergillus terreus transformed artemisinin to two products. They were identified as 1-deoxyartemisinin (2) and 4α-hydroxy-1-deoxyartemisinin (3) on the basis of their spectroscopic data.ConclusionsThe microbial transformation of artemisinin by Aspergillus terreus was investigated, and two products (1-deoxyartemisinin and 4α-hydroxy-1-deoxyartemisinin) were obtained. This study is the first to report on the microbial transformation of artemisinin by Aspergillus terreus.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Microbial transformation of artemisinin by Aspergillus terreus

Zhu

Zhan

2017

Bioresour. Bioprocess.

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“…There are many reports on microbial transformation of artemisinin. These transformations usually include the following metabolic processes: hydroxylation, deoxidation, and acetoxylation reactions (Gaur et al 2014;Parshikov et al 2004bParshikov et al , 2006Zhan et al 2002;Goswami et al 2010). The products of the reported microbial transformations of artemisinin usually include 7β-hydroxyartemisinin, 7β-hydroxy-9α-artemisinin, 4α-hydroxy-1-deoxyartemisinin, 6β-hydroxyartemisinin, 5β-h y d r o x y a r t e m i s i n i n , 4 β -h y d r o x y a r t e m i s i n i n , deoxyartemisinin, 4β-hydroxy-1-deoxyartemisinin, 5aα-hydroxy-1-deoxyartemisinin, 4β-acetoxy artemisinin, 4α-hydroxyartemisinin, and 5aα-hydroxyartemisinin (Parshikov et al 2004b(Parshikov et al , 2006Zhan et al 2002;Goswami et al 2010;Gaur et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…So, it is important to find new and more effective antimalarial drugs by modifying the structure of artemisinin and its analogues through chemical and biological methods. Some studies on the structural modification of artemisinin by chemical and biological methods were reported (Gaur et al 2014;Parshikov et al 2004aParshikov et al , b, 2006Zhan et al 2002;Goswami et al 2010;Acton 1999).…”

Section: Introductionmentioning

confidence: 99%

Biotransformation of artemisinin by Aspergillus niger

Zhan

Liu

et al. 2015

Appl Microbiol Biotechnol

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Biotransformation of artemisinin (1) by Aspergillus niger was investigated. During 12 days at 28 °C and pH 6.0, A. niger transformed artemisinin into four products. They were identified as 3β-hydroxy-4,12-epoxy-1-deoxyartemisinin (2), artemisinin G (3), 3,13-epoxyartemisinin (4), and 4α-hydroxy-1-deoxyartemisinin (5). Products 2 and 4 are new compounds and are being reported here for the first time. The product 4 contains a 3,13-epoxy structure. This is the first report of epoxidation of artemisinin using microbial strains. The product 4 still has an intact peroxide bridge and therefore can be used as a scaffold for further structural modification using chemical and biological methods in the search for new antimalarial drugs.

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Biotransformation of artemisinin to a novel derivative via ring rearrangement by Aspergillus niger

Luo

Mobley

Woodfine

et al. 2022

Appl Microbiol Biotechnol

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Artemisinin is a component part of current frontline medicines for the treatment of malaria. The aim of this study is to make analogues of artemisinin using microbial transformation and evaluate their in vitro antimalarial activity. A panel of microorganisms were screened for biotransformation of artemisinin (1). The biotransformation products were extracted, purified and isolated using silica gel column chromatography and semi-preparative HPLC. Spectroscopic methods including LC-HRMS, GC–MS, FT-IR, 1D and 2D NMR were used to elucidate the structure of the artemisinin metabolites.1H NMR spectroscopy was further used to study the time-course biotransformation. The antiplasmodial activity (IC50) of the biotransformation products of 1 against intraerythrocytic cultures of Plasmodium falciparum were determined using bioluminescence assays. A filamentous fungus Aspergillus niger CICC 2487 was found to possess the best efficiency to convert artemisinin (1) to a novel derivative, 4-methoxy-9,10-dimethyloctahydrofuro-(3,2-i)-isochromen-11(4H)-one (2) via ring rearrangement and further degradation, along with three known derivatives, compound (3), deoxyartemisinin (4) and 3-hydroxy-deoxyartemisinin (5). Kinetic study of the biotransformation of artemisinin indicated the formation of artemisinin G as a key intermediate which could be hydrolyzed and methylated to form the new compound 2. Our study shows that the anti-plasmodial potency of compounds 2, 3, 4 and 5 were ablated compared to 1, which attributed to the loss of the unique peroxide bridge in artemisinin (1). This is the first report of microbial degradation and ring rearrangement of artemisinin with subsequent hydrolysis and methoxylation by A.niger. Key points • Aspergillus niger CICC 2487 was found to be efficient for biotransformation of artemisinin • A novel and unusual artemisinin derivative was isolated and elucidated • The peroxide bridge in artemisinin is crucial for its high antimalarial potency • The pathway of biotransformation involves the formation of artemisinin G as a key intermediate

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In vitro antimalarial studies of novel artemisinin biotransformed products and its derivatives

Cited by 21 publications

References 26 publications

Microbial transformation of artemisinin by Aspergillus terreus

Microbial transformation of artemisinin by Aspergillus terreus

Biotransformation of artemisinin by Aspergillus niger

Biotransformation of artemisinin to a novel derivative via ring rearrangement by Aspergillus niger

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