Structure-activity relationship and molecular modelling studies of quinazolinedione derivatives MMV665916 as potential antimalarial agent
Résumé
A series of new quinazolinedione derivatives have been readily synthesized and evaluated for their in vitro antimalarial growth inhibition activity. Most of the compounds inhibited P. falciparum FcB1 strain in the low to medium micromolar concentration. Compounds 7g, 7i and 7k showed the best inhibitory activity with EC50 values around 5 µM. However, these compounds were less potent than the original hit MMV665916, which showed remarkable growth inhibition with EC50 value of 0.4 µM. In addition, a novel approach for determining the docking poses of these quinazolinedione derivatives with their potential protein target, the P. falciparum farnesyltransferase PfFT, was investigated.
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