Currently used antimalarial drugs are aromatic heterocyclic derivatives, most often containing a basic component with an added alkyl chain in their chemical structure. Although these drugs are effective in therapy, they have many side effects. Thus, new, more effective and safer drugs are sought from other derivative groups, including imidazolidinedione derivatives. Imidazolidinedione derivatives, such as compound WR182393, a 2-guanidinoimidazolidinedione derivative, a cyclic dicarboxamide derivative of Chlorproguanil, are very interesting compounds with antimalarial activity.
This project describes a series of compounds with potential antimalarial activites designed around the imidazolidinedione ring of the WR182393 core, where the imidazolidinedione core was linked via the alkylene chain and the piperazine system (basic component) to the bicyclic system.
These compounds were evaluated against the asexual stages of two strains of Plasmodium falciparum, namely, the chloroquine-sensitive (D10) and chloroquine-resistant (W2) strains. The antiplasmodial effect was stronger against the W2 strain (determined IC50 were in the range of 2.4-5.6 µg/ml) in comparison to the D10 strain (IC50 6.2-9.6 µg/ml).
The synthetized derivatives, possessing enhanced antimalarial activity against the CQ-resistant strain of P. falciparum are promising antimalarial drug candidates. The results also indicate the need for development of appopriate lipid delivery systems due to the highly hydrophobic nature of these active compounds.
The project is co-financed by the Polish National Agency for Academic Exchange, the Italian Ministry of Foreign Affairs and International Cooperation "Executive Programme for Scientific and Technological Cooperation between the Italian Republic and the Republic of Poland" and supported by JUMC grant no N42/DBS/000178.
