Contribution in an anthology

Appeared in: Apicomplexan parasites : molecular approaches toward targeted drug development

Editor list: Becker Katja

Publication year: 2011

Pages: 413-430

ISBN: 978-3-527-32731-7

eISBN: 978-3-527-63388-3

DOI Link: https://doi.org/10.1002/9783527633883.ch22

Title of series: Drug discovery in infectious diseases

Number in series: 2

Abstract: 

Endoperoxides such as artemisinin derivatives are prospective, novel, broad-spectrum apicomplexicidal agents. However, a short plasma half-life, limited bioavailability, poor solubility either in oil or water, and recently reducing susceptibility remain significant challenges. Furthermore, the mechanism of action of endoperoxides remains incompletely understood. A multitarget mechanism of action is proposed, at the center of which is the endoperoxide moiety which, upon reductive cleavage, leads to the formation of highly reactive oxygen- or carbon-centered radicals that attack cellular targets such as the SERCA-type Ca²⁺-ATPase. As a result of efforts to improve their properties, diverse endoperoxides have either been synthesized or extracted from natural sources; however, with the exception of Plasmodium species, they have not been systematically examined in other apicomplexan parasites. In this chapter, recent developments in the field of endoperoxide centered therapy are reviewed, and approaches for rational endoperoxide-based drug development discussed. The data suggest the further development and improvement of drug-hybrids, and advocate the implementation of endoperoxide combination therapies, as already exist for Plasmodium species, also against other apicomplexan parasites.

Harvard Citation style: Kasozi, D., Rahlfs, S. and Becker, K. (2011) Current aspects of endoperoxides in antiparasitic chemotherapy, in Becker Katja (ed.) Apicomplexan parasites : molecular approaches toward targeted drug development. Weinheim: Wiley-Blackwell, pp. 413-430. https://doi.org/10.1002/9783527633883.ch22

APA Citation style: Kasozi, D., Rahlfs, S., & Becker, K. (2011). Current aspects of endoperoxides in antiparasitic chemotherapy. In Becker Katja (Ed.), Apicomplexan parasites : molecular approaches toward targeted drug development (pp. 413-430). Wiley-Blackwell. https://doi.org/10.1002/9783527633883.ch22