Design, Synthesis and Antimalarial Activity of a New Class of Iron Chelators

Title: Design, Synthesis and Antimalarial Activity of a New Class of Iron Chelators

Volume: 2 Issue: 2

Author(s): Kumkum Srivastava, S. B. Katti, Sunil K. Puri, W. Haq and V. R. Solomon

Affiliation:

Keywords: antimalarial agents, 4-aminoquinoline, Iron chelator

Abstract: Iron is crucial for many biochemical reactions involved in the growth and multiplication of the malaria parasite Plasmodium falciparum. There are many reports indicating that the iron chelators have antimalarial activity in vitro, in vivo and in human studies. However, these compounds suffer from a number of serious problems such as limited membrane permeability, short half-life and require long subcutaneous infusions. To circumvent these drawbacks we have designed a new class of iron chelators, wherein EDTA is tethered to 4-aminoquinoline. Here 4-aminoquinoline scaffold is used as a carrier to penetrate biological membrane and facilitate targetting the compounds to acidic food vacuole of the parasite. This study describes the synthesis of novel iron chelators and their in vitro antimalarial activity against P. falciparum strain of NF-54. The calculated LogP values of these compounds suggest the importance of lipophilicity for the antimalarial activity. The EDTA esters are more active than the corresponding acids. The biophysical studies suggest that these compounds may inhibit the parasite growth by iron chelation mechanism.

Cite this article as:

Srivastava Kumkum, Katti B. S., Puri K. Sunil, Haq W. and Solomon R. V., Design, Synthesis and Antimalarial Activity of a New Class of Iron Chelators, Medicinal Chemistry 2006; 2 (2) . https://dx.doi.org/10.2174/157340606776056179