Artemisinin biological activity

Chemistry and biological activity of artemisinin (sesquiterpene y-lactone with oxepane fragment and transannular peroxide bridge) and related antimalari-als 99H(51)1681. 

Ryd6n A-M, Kayser O (2007) Chemistry, biosynthesis and biological activity of artemisinin and related natm-al peroxides. 9 1-31... 

Chemistry, Biosynthesis and Biological Activity of Artemisinin and Related Natural Peroxides A.-M. Ryden O. Kayser... 

The large diversity of biological activities including antimalarial, antioxoplasmosis, antileishmaniasis, antishistosomiasis, antitrypanosomiasis, antiviral, antifugal and even anticancer activities displayed by artemisinin and artemisinin derivatives (cf. Ref. 55 for a review) added to the multitude of artemisinin-inspired trioxanes, trioxolanes, tetraoxa-cycloalkanes and peroxide, homodimeric-, trimeric- and even tetrameric artemisinin derivatives recently designed and synthesized is a clear indication that in the future, these compounds will become even more important in the chemotherapy of various diseases, perhaps even above and beyond those mentioned here. 

Bhattacharya AK and Sharma RP (1999) Recent developments on the chemistry and biological activity of artemisinin and related antimalarials - an update. 

Further, there does not exist sufficient data regarding the biological activity for each enantiomer in a racemic mixture of artemisinin analogues. To help define the antimalarial contribution made by each enantiomer, a model was developed in which 40 racemates were placed as single (+)-enantiomers in the original database of 202 compounds. By doing this it was implied that the (-)-enantiomers are as active as their counterpart, and an optically pure compound is not necessary for antimalarial activity. These achiral models have been discussed as 199 (2 A/C.3) and 199 Dock. A database without the racemates, or chiral models 160 (2 A/C.3) and 160 Dock, were also included in our study. Finally, adjustment to an achiral model was attempted in which the activities of the racemates in the 199 (2 A/C.3) model were multiplied by 2, or model 199 (2 A/C.3). In each case, data was subjected to the statistical pis analysis (Table 18). Relative antimalarial activities were predicted for two racemic compounds 421 and 422,155 using these datasets as shown in Tables 19 and 20. 

Guha R, Jurs PC (2004) The development of QSAR models to predict and interpret the biological activity of artemisinin analogues. J Chem Inf Comput Sci 44 1440-1449... 

Haynes, R. K. Ho, W.-Y Chan, H.-W. Fugmann, B. Stetter, J. Croft, S. L. Vivas, L. Peters, W. Robinson, B. L. Highly antimalaria-active artemisinin derivatives Biological activity does not correlate with chemical reactivivty. Angew. Chem. Int. Ed., 2004, 43 1381-1385. 

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/. 

Fig. 4. HCA dendogram for artemisinin and derivatives (training set) with biological activity against human hepatocellular carcinoma HepG2. Plus sign for more active compounds while minus sign for less active ones...

Quassinoids have attracted much attention due to the wide spectrum of biological activities that they display, viz., antimalarial, antifeedant, anti-inflanunatory, antiulcer, antipyretic, antifertility, antileukemic, cytotoxic activities, and induction of murine stem cell differentiation which have been widely reported [54-59]. We have demonstrated that quassin is a potent immunomodulatory tool that efficiently controls the estabhshment of leishmanial parasite within the host macrophages [60]. Our contention was that quassin could be used as a potential inununomodulator to generate the required immunity not only for the treatment of leishmaniasis but also for the treatment of other chronic infectious diseases. Subsequently, we had shown that both quassin and neoquassin can be used along with artesunate (a derivative of artemisinin) as combinatorial therapy against malaria [61]. 

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