New Antimalarial Drugs

Abstract

Approximately 40% of the world population live in areas with the risk of malaria. Each year, 300-500 million people suffer from acute malaria, and 0.5-2.5 million die from the disease. Although malaria has been widely eradicated in many parts of the world, the global number of cases continues to rise. The most important reason for this alarming situation is the rapid spread of malaria parasites that are resistant to antimalarial drugs, especially chloroquine, which is by far the most frequently used. The development of new antimalarial drugs has been neglected since the 1970s owing to the end colonialism, changes in the areas of military engagement, and the restricted market potential. Only in recent years, in part supported by public funding programs, has interest in the development of antimalarial drugs been renewed. New data available from the recently sequenced genome of the malaria parasite Plasmodium falciparum and the application of methods of modern drug design promise to bring significant development in the fight against this disease.

Molecular docking and 3D-quantitative structure activity relationship analyses of peptidyl vinyl sulfones: Plasmodium Falciparum cysteine proteases inhibitors

“…• Compounds that orient any hydrophobic part of R 3 group towards Tyr78 and Leu84 would exhibit enhanced FP2 inhibitory activity.…”

“…There is known, widespread resistance to once highly effective but now virtually useless antimalarials, like the well-known example of chloroquine [1][2][3]. The increasing resistance of malaria parasites is a key factor in the persistence of malaria as a global major health concern [4].…”

Synthesis of α‐Substituted Fosmidomycin Analogues as Highly Potent Plasmodium falciparum Growth Inhibitors.

“…As a result of the resurgence of malaria and increased resistance to prevalent antimalarials such as chloroquine, there is an urgent need for new efficient chemotherapeutics against this disease. 1 [ Figure 1] Drug development has shifted toward targeting specific proteins that are unique and critical for cellular growth and survival of the parasite. 2,3 Recently, the presence of a mevalonate-independent pathway for isoprenoid biosynthesis in P. falciparum was discovered.…”

The mechanism of antimalarial action of the ruthenium(II)–chloroquine complex [RuCl2(CQ)]2

“…Four different parasites of the Plasmodium genus affect humans-P. falciparum, P. vivax, P. malariae, and P. ovale; the first two are the most common and P. falciparum causes the most deadly form of the disease [1,2]. Since the discovery and purification of quinine from the bark of the cinchona tree, several antimalarial drugs have become available, notably quinolines [chloroquine (CQ), amodiaquine, mefloquine, primaquine], inhibitors of enzymes required for folate metabolism (pyrimethamine/sulfadoxine, proguanil), and endoperoxides derived from the natural product artemisinin [3][4][5][6]. CQ ( Fig.…”