» Articles » PMID: 7937560

Microbial and Mammalian Metabolism Studies of the Semisynthetic Antimalarial, Anhydrodihydroartemisinin

Overview
Journal Pharm Res
Specialties Pharmacology
Pharmacy
Date 1994 Jul 1
PMID 7937560
Citations 2
Authors
Affiliations
Soon will be listed here.
Abstract

Microbial metabolism studies of the semisynthetic antimalarial anhydrodihydroartemisinin (1), have shown that it is metabolized by a number of microorganisms. Large scale fermentation with Streptomyces lavendulae L-105 and Rhizopogon species (ATCC 36060) have resulted in the isolation of four microbial metabolites. These metabolites have been identified as a 14-carbon rearranged product (2), 9 beta-hydroxyanhydrodihydroartemisinin (3), 11-epi-deoxydihydroartemisinin (4), and 3 alpha-hydroxydeoxyanhydrodihydroartemisinin (5). Microbial metabolites were completely characterized by spectral methods, including 1H-NMR and 13C-NMR spectroscopy. The structure and stereochemistry of metabolite 2 were unequivocally established by X-ray crystallographic analysis. Thermospray mass spectroscopy/high-performance liquid chromatographic analyses of plasma from rats used in mammalian metabolism studies of 1 have shown microbial metabolite 3 to be the major mammalian metabolite. In vitro antimalarial testing has shown metabolite 3 to possess antimalarial activity.

Citing Articles

Inhibition of prostate cancer cell line (PC-3) by anhydrodihydroartemisinin (ADHA) through caspase-dependent pathway.

Ahmad F, Sarder A, Gour R, Karna S, Arora P, Ravindranathan Kartha K EXCLI J. 2020; 19:613-619.

PMID: 32483407 PMC: 7257247. DOI: 10.17179/excli2020-1331.


Comparison of 3D quantitative structure-activity relationship methods: analysis of the in vitro antimalarial activity of 154 artemisinin analogues by hypothetical active-site lattice and comparative molecular field analysis.

Woolfrey J, Avery M, Doweyko A J Comput Aided Mol Des. 1998; 12(2):165-81.

PMID: 9690175 DOI: 10.1023/a:1007967517859.

References
1.
Klayman D . Qinghaosu (artemisinin): an antimalarial drug from China. Science. 1985; 228(4703):1049-55. DOI: 10.1126/science.3887571. View

2.
Elmarakby S, Clark A, Baker J, Hufford C . Microbial metabolism of bornaprine, 3-(diethylamino)propyl 2-phenylbicyclo[2.2.1]heptane-2-carboxylate. J Pharm Sci. 1986; 75(6):614-8. DOI: 10.1002/jps.2600750620. View

3.
Smith R, Rosazza J . Microbial models of mammalian metabolism. J Pharm Sci. 1975; 64(11):1737-59. DOI: 10.1002/jps.2600641104. View

4.
Clark A, Hufford C . Use of microorganisms for the study of drug metabolism: an update. Med Res Rev. 1991; 11(5):473-501. DOI: 10.1002/med.2610110503. View

5.
Lee I, Hufford C . Metabolism of antimalarial sesquiterpene lactones. Pharmacol Ther. 1990; 48(3):345-55. DOI: 10.1016/0163-7258(90)90053-5. View