Microbial Metabolism Studies of the Antimalarial Sesquiterpene Artemisinin

Abstract

Microbial metabolism of the sesquiterpene lactone antimalarial drug artemisinin [1] was studied. Screening studies have shown a number of microorganisms capable of metabolizing artemisinin [1]. Scale-up fermentation with Nocardia corallina (ATCC 19070) and Penicillium chrysogenum (ATCC 9480) have resulted in the production of two major microbial metabolites that have been characterized with the use of 2D-nmr techniques. These metabolites have been identified as deoxyartemisinin [2] and 3 alpha-hydroxydeoxyartemisinin [3].

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

“…In the EI mass spectra it showed molecular ion peak at 266 consistent with the molecular formulae C 15 H 22 O 4 and further fragmentation pattern clearly indicating it as deoxyartemisinin. The compound's 1 H and 13 C NMR and different 2D spectral data were well in agreement with the earlier published reports [4].…”

“…A. flavus was found to transform artemisinin to deoxyartemisinin in higher yield (30.5%) than the previous reports [4,15,31]. The biotransformed product was characterized by NMR, IR and Mass spectroscopy.…”

“…The metabolism, chemical transformation, thermal rearrangement and decomposition studies of artemisinin were well established [3,4]. Among known antimalarial compounds, artemisinin has a novel structure with a unique 1,2,4-trioxane ring system.…”

“…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].…”

“…Studies on the microbial transformation of artemisinin with Nocardia corollina, Penicillium chrysogenum, Mucor polymorphus, Cunninghamella echinulata, Mucor ramannianus, Eurotium amstelodami, Streptomgillus niger, Cunninghamella elegans yielded 3α-hydroxydeoxyartemisinin, deoxyartemisinin, artemisitone-9, 4α-hydroxyartemisinin, 7β-hydroxyartemisinin, 6-hydroxyartemisinin, 5β-hydroxyartemisinin, 9β-hydroxyartemisinin, 3β-hydroxyartemisinin, 3β-hydroxydeoxyartemisinin, 1α-hydroxydeoxyartemisinin, 7β-hydroxy-9α-artemisinin, 4α-hydroxy-1-deoxoartemisinin, 10β-hydroxyartemisinin and 3α-hydroxydeoxyartemisinin respectively [4,[15][16][17][18][19][20]. The importance and usefulness of microbial transformation in carrying out a variety of chemical conversions is well documented in the previously published reports [21,22].…”