Current Topics in Medicinal Chemistry - Volume 12, Issue 5, 2012

For centuries, the human race has been fighting the devastating effects of malaria, caused by the parasite Plasmodium. In 2009, there were 225 million cases of malaria resulting in 781,000 deaths according to the World Health Organization (WHO) [1]. Significant strides towards eradication were made during the early to mid-1900s through the introduction of fast-acting antimalarial agents such as chloroquine (CQ), sulphado Read More

The present review describes the development of synthetic cyclic peroxides, which are designed to surpass the antimalarial activity of the lead molecule, the natural product (+)-artemisinin and some of its C10 derivatives. To begin with, tricyclic and bicyclic 1,2,4-trioxanes are taken to show how the pharmacophore was identified and chirality proved to be irrelevant. The action of ferrous salts on trioxanes illustrates the struct Read More

This short review tells the story of how Reversed Chloroquine drugs (RCQs) were developed. These are hybrid molecules, made by combining the quinoline nucleus from chloroquine (CQ) with moieties which are designed to inhibit efflux via known transporters in the membrane of the digestive vacuole of the malaria parasite. The resulting RCQ drugs can have potencies exceeding that of CQ, while at the same time having physic Read More

Falcipains are Plasmodium falciparum cysteine proteases involved in different processes of the erythrocytic cycle of the malaria parasite like hydrolysis of host hemoglobin, erythrocyte invasion, and erythrocyte rupture. These proteases constitute promising targets in the search for novel therapies that would ease the burden caused by the increasing resistance to current antimalarial drugs. Despite biochemical characteriz Read More

Plasmepsins are the aspartic proteases of Plasmodium that play key roles in the survival of the parasite in its host. The plasmepsins of the digestive vacuole play an important role in hemoglobin degradation, providing the parasite with a vital source of nutrients. Recently, plasmepsin V has been shown to be an essential protease, processing hundreds of parasite proteins for export into the host erythrocyte. The functions of the re Read More

Millions of deaths each year are attributed to malaria worldwide. Transmitted through the bite of an Anopheles mosquito, infection and subsequent death from the Plasmodium species, most notably P. falciparum, can readily spread through a susceptible population. A malaria vaccine does not exist and resistance to virtually every antimalarial drug predicts that mortality and morbidity associated with this disease will increase. Read More

Antimalarial drug discovery has historically benefited from the whole-cell (phenotypic) screening approach to identify lead molecules in the search for new drugs. However over the past two decades there has been a shift in the pharmaceutical industry to move away from whole-cell screening to target-based approaches. As part of a Wellcome Trust and Medicines for Malaria Venture (MMV) funded consortium to discover new b Read More