Flowcytometric evaluation of Riminophenazines as antimalarial agents

The in vitro antimalarial activity of clofazimine and seven of its analoques, all TMP(tetramethyl-piperidyl group)-derivatives except B669, against the RB-1 and pfUP-1 laboratory strains of Plasmodium falciparum was investigated using a flow cytometric procedure. The flow cytometric method was compared with microscopy and radiometry for efficiency in quantitating the level of parasitemia in malaria cultures. The flow cytometric method compared well, as determined by the Bland and Altman measure of agreement, with both microscopy and radiometry (includes a fixing step that allows samples to be evaluated at any one time). The riminophenazine agents were found to exhibit antimalarial action of varying degrees: the B669, B4100, B4103, B4112 and B4158 showed the best activity followed by B4121 and B4169. Clofazimine did not exhibit any activity at concentrations up to 2ug/ml in this system. Their effective concentrations in vitro were comparable to that of standard antimalarial agent chloroquine. The agents B4103 and B4112 exhibited additive antimalarial activities when combined with chloroquine.