Opportunities and Challenges in Antiparasitic Drug Discovery

Abstract

New antiparasitic drugs are urgently needed to treat and control diseases such as malaria, leishmaniasis, sleeping sickness and filariasis, which affect millions of people each year. However, because the majority of those infected live in countries in which the prospects of any financial return on investment are too low to support market-driven drug discovery and development, alternative approaches are needed. In this article, challenges and opportunities for antiparasitic drug discovery are considered, highlighting some of the progress that has been made in recent years, partly through scientific advances, but also by more effective partnership between the public and private sectors.

Blood schizontocidal activity of methylene blue in combination with antimalarials againstPlasmodium falciparum

“…With the emergence and spread of drug resistance in malaria endemic regions, combination therapy represents an effective approach in curbing the development of resistance of the parasite to the commercially available compounds (Gupta et al, 2002). Additionally it may reduce toxicity and shorter treatment regimens (Pink et al, 2005). Akoachere et al (2005) found MB to be antagonistic with AMO, CQ, PRIM and PYR; additive with MEF and Q; synergistic with ART, artemisinin and artesunate, against P. falciparum K1 strain in culture.…”

“…didate must be effective within a three-day regimen, safe in small children (< 6 months) and pregnant women, easy to package, cheap and have a low propensity to generate resistance (Baird, 2005;Pink et al, 2005). Adapted to oral administration, MB gathers all these features except one: it is not new anymore.…”

Malaria parasite carbonic anhydrase: inhibition of aromatic/heterocyclic sulfonamides and its therapeutic potential

“…Indeed, pfCA catalyzes the formation of HCO 3 -, serving as a substrate for the first enzyme in the pyrimidine biosynthetic pathway, carbamoylphosphate synthetase II. Thus, inhibitors of pfCA may affect the entire biosynthetic pathway, leading to antimalarials which possess a different mechanism of action as compared to the presently known drugs, most of which are rather toxic and led to the emergence of drug-resistance [3,7,8] .…”

“…P. malariae is found worldwide with relatively low frequency, while the least common parasites are P. ovale and P. knowlesi [5] . In addition to the lack of effective vector control and vaccine, the limitation and toxicity of antimalarial drugs in current use, and the spread of drug-resistant malaria parasites accompanied by a worldwide resurgence of malaria highlights the need to develop quickly more effective and less toxic new antimalarial drugs with different mechanism of action [7,8] . This includes the emergence of resistance to artemisinin, the world's best drug to eradicate malaria [9] .…”

Discovery of Novel Benzoxaborole-Based Potent Antitrypanosomal Agents

“…3 There is an urgent need to develop new therapies with low toxicity, improved efficacy, and affordable cost. 4,5 We report here the discovery and structure-activity relationship (SAR) of novel benzoxaborole antitrypanosomal agents. During an initial screening of a focused library of antiinfective benzoxaboroles, compound 12 was found to inhibit in vitro T. brucei growth (IC 50 = 0.12 μg/mL).…”