| Dihydroartemisinin | |
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(3R,5aS,6R,8aS,9R,12S,12aR)-decahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin-10-ol |
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Other names
DHA |
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| Identifiers | |
| CAS number | 71939-50-9 |
| PubChem | 107770 |
| ChemSpider | 96929 |
| UNII | 6A9O50735X |
| ChEMBL | CHEMBL25164 |
| Beilstein Reference | 4185848 |
| Jmol-3D images | Image 1 Image 2 |
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| Properties | |
| Molecular formula | C15H24O5 |
| Molar mass | 284.35 g mol−1 |
| (verify) (what is: /?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) |
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| Infobox references | |
Dihydroartemisinin (or dihydroqinghaosu or artenimol) is a drug used to treat malaria. Dihydroartemisinin is the active metabolite of all artemisinin compounds (artemisinin, artesunate, artemether, etc.) and is also available as a drug in itself. It is a semi-synthetic derivative of artemisinin and is widely used as an intermediate in the preparation of other artemisinin-derived antimalarial drugs.[1]It is sold commercially in combination with piperaquine and has been shown to be equivalent to artemether/lumefantrine.[2]
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The lactone of artemisinin could selectively be reduced with mild hydride-reducing agents, such as sodium borohydride, potassium borohydride, and lithium borohydride to dihydroartemisinin (a lactol) in over 90% yield. It is a novel reduction, because normally lactone cannot be reduced with sodium borohydride under the same reaction conditions (0-5 ˚C in methanol). Reduction with LiAlH4 leads to some rearranged products. It was surprising to find that the lactone was reduced, but that the peroxy group survived. However, the lactone of deoxyartemisinin resisted reduction with sodium borohydride and could only be reduced with diisobutylaluminium hydride to the lactol deoxydihydroartimisinin. These results show that the peroxy group assists the reduction of lactone with sodium borohydride to a lactol, but not to the alcohol which is the over-reduction product. No clear evidence for this reduction process exists.
Dihydroartemisinin is available as a fixed drug combination with piperaquine (each tablet contains 40 mg of dihydroartemisinin and 320 mg of piperaquine; trade name Artekin, manufactured by Holleykin Pharmaceuticals).
The adult dose is 1.6/12.8 mg/kg per dose (rounded up or down to the nearest half tablet) given at 0 h, 8 h, 24 h, and 48 h. Alternatively, the same total dose may be given once daily for three days.[3]
Dihydroartemisinin is also sold in Africa as Cotecxin in 60 mg tablets, which is manufactured by Zhejiang Holley Nanhu Pharmaceutical Co., Ltd., in China.
Accumulative research suggests that dihydroartemisinin and other artemisinin-based endoperoxide compounds may display activity as experimental cancer chemotherapeutics.[4] Recent pharmacological evidence demonstrates that dihydroartemisinin targets human metastatic melanoma cells with induction of NOXA-dependent mitochondrial apoptosis that occurs downstream of iron-dependent generation of cytotoxic oxidative stress.[5]
In combination with piperaquine:
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