Discovery and optimisation studies of antimalarial phenotypic hits

作者：Mital Alka; Murugesan Dinakaran; Kaiser Marcel; Yeates Clive; Gilbert Ian H^*

来源：European Journal of Medicinal Chemistry, 2015, 103: 530-538.

DOI：10.1016/j.ejmech.2015.08.044

• Plasmodium falciparum
• Malaria
• Medicinal chemistry
• Phenotypic hit

There is an urgent need for the development of new antimalarial compounds. As a result of a phenotypic screen, several compounds with potent activity against the parasite Plasmodium falciparum were identified. Characterization of these compounds is discussed, along with approaches to optimise the physicochemical properties. The in vitro antimalarial activity of these compounds against P. falciparum K1 had EC50 values in the range of 0.09-29 mu M, and generally good selectivity (typically >100-fold) compared to a mammalian cell line (L6). One example showed no significant activity against a rodent model of malaria, and more work is needed to optimise these compounds.

• 出版日期2015-10-20