Artemisinin derivatives

Artemisinin, and its semi-synthetic derivatives are a group of drugs used against Plasmodium falciparum malaria.[1]

It is isolated from the plant Artemisia annua, sweet wormwood, a herb employed in Chinese traditional medicine. Artemisinin was discovered by a Chinese scientist, Tu Youyou, who was awarded half of the 2015 Nobel Prize in Medicine for her discovery.[2]

Treatments containing an artemisinin derivative (artemisinin-combination therapies, ACTs) are now standard treatment worldwide for P. falciparum malaria.[3]

Its dimers or trimers which have been invented the scientist of Friedrich-Alexander-Universität Erlangen-Nürnberg have increased in vitro activity against Plasmodiumfalciparum 3D7 strain, leukemia cells (CCRF-CEM and multidrug-resistant subline CEM/ADR5000) and human cytomegalovirus (HCMV). [4]

Trimer TF 27 displays superior potency against both leukemia cell lines (IC50 up to 0.002 μM for CCRF-CEM and IC50 up to 0.20 μM for CEM/ADR5000) and is even more active than clinically used doxorubicin (IC50 1.61 μM for CEM/ADR5000).

With respect to anti-HCMV activity, this trimer is the most efficient hybrid (IC50 0.04 μM) outperforming ganciclovir (IC50 2.6 μM), dihydroartemisinin (IC50 >10 μM) and artesunic acid (IC50 3.8 μM).

The following derivatives are available:

 

Artemisinin

Dihidro-Artemisinin

Acetoxy- Dihidro-Artemisinin (TF 1)

Artesunic acid

Trimer Artemisinin (TF 27)

 

 

 

 

[1] White NJ (July 1997). “Assessment of the pharmacodynamic properties of antimalarial drugs in vivo”. Antimicrob. Agents Chemother. 41 (7): 1413–22. PMC 163932 Freely accessible. PMID 9210658.

[2] “The Nobel Prize in Physiology or Medicine 2015″ (PDF). Nobel Foundation.

[3] Guidelines for the Treatment of Malaria. Geneva: World Health Organization. 2006. ISBN 92-4-154694-8.

[4] Highly potent artemisinin-derived dimers and trimers: Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities. Bioorg Med Chem. 2015 Sep 1;23(17):5452-8. doi: 10.1016/j.bmc.2015.07.048.