Dorota Rusek, Dariusz Kurzynoga, Jerzy Mikołajczyk, Tadeusz Głąbski
Nowe możliwości terapii malarii
New possibilities for treatment of malaria
Malaria is the third, after tuberculosis and AIDS, the most serious disease causing nearly one million deaths annually, mostly in Africa south of the Sahara. The disease is particularly severe in children below the age of 5 years. It is an enormous public health problem. Caused by a single-celled parasite Plasmodium, malaria is transmitted from person to person by bite of female Anopheles mosquitoes. Until now no vaccines or 100 per cent effective chemotherapeutics have been available against all Plasmodium spp. in all endemic area. The parasite has progressively developed resistance to most of the available antimalarials such as quinine, mefloquine, chloroquine in many endemic regions. It necessitated the search of novel drugs. At the present WHO recommended Artemisinin Combination Therapy (ACT) as the first line treatment of uncomplicated P. falciparum in place of monotherapy. Further intensive works resulted in a new potential antimalarials, a completely synthetic ozonide, based upon the 1,2,4-trioxolane pharmacophore. The new drugs currently during clinic tests are: arterolan (OZ277) (Phase III Clinical trials as combination product with piperaquine) and OZ439 (Phase IIa), a promising candidate as a single-dose oral antimalarial drug. They exibit a rapid onset of action, potent activity against all blood stages of P. falciparum and P. vivax, high oral bioavailability, good safety profile and low cost of manufacturing. Next generation antimalarial drugs are hybrid molecules with dual functionality development and/or multitherapeutic strategies, which utilize new chemical entities with two or more different pharmacophores.
Keywords: malaria, Artemisinin Combination Therapy (ACT), 1,2,4-trioxolane, arterolan (OZ277), OZ439.
© Farm Pol, 2011, 67(10): 705-715