Mjbs 6(1-2).indd

Mongolian Journal of Biological Sciences 2008 Vol. 6(1-2): 45-49 Calculation of Quantitative Structure-Activity Relationship Descriptors
of Artemisinin Derivatives
Jambalsuren Bayarmaa1 and Vladimir Frecer2
1Department of Biochemistry and Bioorganic Chemistry, Faculty of Biology, National University of Mongolia E-mail: bayarmaa_j@biology.num.edu.mn 2Area of Pure and Applied Chemistry, International Center for Sciense and High Technology-UNIDO, Trieste, Italy E-mail: vladimir.frecer@ics.trieste.it Abstract
Quantitative structure-activity relationships are based on the construction of predictive models using a set of known molecules and associated activity value. This accurate methodology, developed with adequate mathematical and computational tools, leads to a faster, cheaper and more comprehensive design of new products, reducing the experimental synthesis and testing on animals. Preparation of the QSAR models of artemisinin derivatives was carried out by the genetic function algorithm (GFA) method for 91 molecules. The results show some relationships to the observed antimalarial activities of the artemisinin derivatives. The most statistically signifi cant regression equation obtained from the fi nal GFA relates to two molecular descriptors. Key words: molecular model, descriptor, QSAR technique, artemisinin derivatives
Introduction
Artemisinin and its derivatives are only the group of compounds that is still effective against drug- Malaria is one of the most serious parasitic resistant P. falciparum strains, and has the ability diseases in the world. There are millions of acute to quickly reduce parasite level (Krishna, 2004). cases of malaria each year globally, resulting in From the other side, it has short plasma half-life, more than one million deaths. The clinical disease limited bioavailability, poor solubility in oil and caused by Plasmodium falciparum is widely water, and the low yield from natural sources distributed and entrenched in areas of the world where climates are suitable for its transmission. to develop new chemotherapeutic artemisinin The present level of annual global malaria incident derivatives. By the chemical modifi cation of consisted of about 500 million, 350 million in the artemisinin at the position of C10 semisynthetic African region and 125 million in the South East derivatives as artesunate, artemether, artelinic Asian region. Deaths due to malaria are occurring acid and dihydroartemisinin were produced, in increasing numbers because of frequent failure which have more antimalarial activities in of the conventional treatments using drugs such vitro than artemisinin itself (Pinheiro, 2003). as chloroquine, mefl oquine and sulfadoxine- Many derivatives have been synthesized using pyrimethamine, against P. falciparum, the dihydroartemisinin by adding different radicals populations of which have developed a high on its rings. But, the development of a new drug is degree of resistance.
a very long and expensive process. To overcome Combination therapies with formulations these diffi culties scientists start to use a variety containing an artemisinin compound have of computational methods to identify novel emerged as a more reliable treatment option. compounds, design compounds with increased Artemisinin is naturally formed in Artemisia selectivity, effi cacy and safety and develop annua L (sweet wormwood). This herb of the compounds into clinical trial candidates. One Asteraceae family has been used for treatment of these methods is the Quantitative Structure-of fever and malaria in China over many Activity Relationship (QSAR) technique. The centuries. Additional names found in China for present work is related to the design of a new artemisinin are qinghaosu and huanghuahaosu. antimalarial active artemisinin analog.

Source: http://mjbs.100zero.org/archive/abstracts/Vol006Issue01-02_Abstracts/mjbs006-01-02-06a.pdf