1α-Hydroxyarteether, a New Microbial Transformation Product

Abstract

The antimalarial drug arteether [1] was subjected to microbial metabolism using Cunninghamella elegans (ATCC 9245) and Streptomyces lavendulae (L-105). 1 tx-Hydroxy arteether[2], a novel microbial metabolite of 1 was isolated from the cultures of C. elegans and fully characterized. The stereochemistry of 2 was established by X-ray crystallographic analysis. 9ß-Hydroxyarteether [3] was isolated from the same culture in a much higher yield (40%) than previously reported (2.2%). Compound 6, a known metabolite of 1, was isolated, from the fermentation cultures of S. lavendulae for the first time.Arteether [1] is the ethyl ether derivative of dihydroartemisinin, a NaBH4 reduction product of artemisinin.

Biotransformation of Artemisinin Mediated through Fungal Strains for Obtaining Derivatives with Novel Activities

“…But, the utility of artemisinin is limited in the biological systems due to its toxicity and water insolubility [5,6]. Studies on modification of artemisinin through biological [4,[7][8] and chemical methodologies [9,10] have been reported [11] to yield more effective and water soluble derivatives. Studies on quantitative structure activity relationship of artemisinin suggest that the structural modification of sesquiterpene lactone may yield desirable antimalarial analogues [12][13][14].…”

Microbial Metabolism of Artemisinin by Mucor polymorphosporus and Aspergillus niger

“…4,5 As an antimalarial drug, artemisinin has the disadvantages of high recrudescence rate and poor solubility in water. Some studies on the modification of artemisinin (1) and its analogues by biological [6][7][8][9][10][11][12] and chemical methods [13][14][15][16][17][18][19][20] have been reported to yield more effective drugs such as artemether in recent years. 21 Because knowledge of mammalian metabolism is an essential feature of artemisinin's clinical pharmacology, microbial metabolism studies have been established as in vitro models to predict the mammalian metabolites of artemisinin and its derivatives (1).…”

Development of a Specific Monoclonal Antibody-Based ELISA to Measure the Artemether Content of Antimalarial Drugs

“…A challenge for the chemical derivitization is the possible breakdown of the peroxide bridge and thus loss of structural similarity between the hapten and the target analyte. Artemether can be readily bio-transformed by C. elegans to produce 9-hydroxyartemether [15] and Streptomyces griseus (ATCC 13273) to produce artemisitone-9 [19] . 9-Hydroxyartemether can readily react with succinic anhydride to yield 9-O-succinylartemether.…”