Artemisinin structure-activity relationship

The antiproliferative structure-activity relationships of 96 artemisinin derivatives are also discussed. 

FDA) for use in humans to treat malaria because this drug is considered a safe drug with few side effects.These features prompted various scientists around the world to evaluate the potential of artemisinin (1) and derivatives to control cancer cells proliferation. This chapter reviews the recent advances on analytical methods for extraction and quantification of artemisinin (1) from A. annua. Examples of artemisinin-derivatives with antiproliferative activities are listed, describing the structure-activity relationships of 96 compounds. This knowledge is essential for future development and use of artemisinin derivatives in cancer therapy. The mechanism of action of artemisinin and derivatives on cancer cells have been well reviewed in literature and therefore is not discussed in this chapter. 

Posner and coworkers have developed versatile methodology for the synthesis of novel 1,2,4-trioxanes that has allowed detailed investigation of their Structure-Activity Relationships (SAR) , while Jefford and coworkers first synthesized fenozan BO-7, so naturally some of their work has centered on its mechanism of action. Avery and coworkers have also contributed significantly to the area by the syntheses and QSAR (Quantitative SAR) studies of many artemisinin analogues. 

Structure-Activity Relationships of Peroxide-Based Artemisinin Antimalarials... 

Avery, M.A., Gao, F., Chong, W.K.M., Mehrotra, S., and Milhous, W.K. Structure-activity relationships of the antimalarial agent artemisinin. I. Synthesis and comparative molecular field analysis of C-9 analogs of artemisinin and 10-deoxoartemisinin, J. Med. Chem., 36, 4264, 1993. 

NMR ( H, 13C), mass spectrometry, infrared (IR), and ultraviolet (UV) were used, especially NMR, in studying the complexation interactions of artemisinins with agents, such as /3-cyclodextrin <2004JPS2076> and micellar dispersions of octanoyl-6-O-ascorbic acid <2002JPS2265>. Furthermore, the structure-activity relationship of solution structures of deoxoartemisinin 10a and carboxypropyldeoxoartemisinin 10b, as antitumor compounds, was studied by H and 13C NMR <2000BBR359>. 

SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIPS OF PEROXIDIC ANTIMALARIALS BASED ON ARTEMISININ... 

In summary, a stereoselective 10-step total synthetic route to the antimalarial sesquiterpene (+)-artemisinin (1) was developed. Crucial elements of the approach included diastereoselective trimethylsilylanion addition to a,p-unsaturated aldehyde 16, and a tandem Claisen ester-enolate rearrangement-dianion alkylation to afford the diastereomerically pure erythro acid 41. Finally, acid 41 was converted in a one-pot procedure involving sequential treatment with ozone followed by wet acidic silica gel to effect a complex process of dioxetane formation, ketal deprotection, and multiple cyclization to the natural product (+)-artemisinin (1). The route was designed for the late incorporation of a carbon-14 label and the production of a variety of analogues for structure-activity-relationship (SAR) studies. We were successful in preparing two millimoles of l4C-l73 which was used for conversion to I4C-arteether for metabolism75 and mode of action studies.76,77... 

Avery, M. A. Alvimgaston, M. Woolfrey, J. R. Synthesis and structure-activity -relationships of peroxidic antimalarials based on artemisinin. Advanc. Medicinal Chem.,... 

Avery MA, McLean G, Edwards G, Ager A. Structure-activity relationships of peroxide-based artemisinin antimalarials. In Biologically Active Natural Products Pharmaceuticals. Cutler SI, Cutler HG, eds. 2000. CRC Press, Boca Raton, EL, pp. 121-132. Pareek A, Nandy A, Kochar D, Patel KH, Mishra SK, Mathur PC. Efficacy and safety of f -arteether and a/f -arteether for treatment of acute Plasmodium falciparum malaria. Am. J. Trop. Med. 2006 75 139-142. http //mednet3.who.int/EMUb/. 

Woolfrey, J.R., Avery, M.A. and Doweyko, A.M. (1998) 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./. Comput. Aid. Mol. Des., 12, 165-181. 

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