Authors: Walsh, J. J.; Bell, A.

Source: Current Pharmaceutical Design, Volume 15, Number 25, September 2009 , pp. 2970-2985(16)

Publisher: Bentham Science Publishers

Abstract:

Malaria continues to devastate much of the tropics and sub-tropics in spite of the availability of a number of antimalarial drugs. Part of this problem is due to the disadvantages of the drugs in use, which include (depending on the drug) side effects, reduced efficacy due to resistance, and high cost. Multiple traditional and novel approaches to the discovery and design of new antimalarial agents are likely to be required to furnish the new drugs necessary for improved malaria control. This review will address one novel and emerging approach, namely the development of hybrid antimalarial agents composed of two distinct antimalarial moieties joined covalently. Particular emphasis will be placed on the properties of the hybrids' design, including biological activity, advantages over other approaches, and the potential to address issues relating to resistance, solubility and formulation/delivery. The review will discuss the synthetic methodology used to form the hybrid and the ease by which it may be cleaved to form the independent components in vivo. The molecules discussed include hybrids of (i) artemisinins or other endoperoxide-based agents and quinolines (e.g. trioxaquines), (ii) chloroquine or other aminoquinolines and resistance-reversing or other agents, and (iii) peptidase inhibitors and other agents. The actual and potential advantages and disadvantages of such hybrids in relation to established single drugs or drug combinations will be discussed critically and promising future directions highlighted.

Keywords: Malaria; Plasmodium falciparum; resistance; hybrid drugs; chloroquine; artemisinin; trioxaquines

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138161209789058183

Affiliations: 1: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.

Publication date: 2009-09-01

More about this publication?

• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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