Examination of the Cytotoxic and Embryotoxic Potential and Underlying Mechanisms of Next-Generation Synthetic Trioxolane and Tetraoxane Antimalarials

Table 1 Cytotoxicity of RKA182, FBEG100, ARS and deoxy-ARS toward a panel of human cells and antimalarial activities versus P. falciparum.

Cell type	RKA182	FBEG100	ARS	Deoxy-ARS
HL-60	11.6 ± 4.0^a	40.6 ± 3.0	2.2 ± 0.2	>100
HEK293T	14.7 ± 0.2	37.1 ± 2.5	20.1 ± 3.4	>100
HepG2	25.5 ± 5.3	58.8 ± 10.8	77.2 ± 17.2	>100
HeLa	37.7 ± 5.5	55.2 ± 5.6	87.8 ± 11.4	>100
RBC	28.0 ± 7.3	>100	18.9 ± 3.7	>100
PBMC	46.6 ± 0.7	56.8 ± 2.1	>100	>100
P. falciparum (3D7)	4.9 ± 1.2 nmol/L^b,c	1.4 ± 0.3 nmol/L	1.8 ± 0.6 nmol/L^c	ND

ND, not determined.
^aIC₅₀ values (µmol/L) were calculated from ATP assay concentration-response curves (Supplementary Figure S3) following incubation with the indicated compound for 24 h. Data represent mean ± SD, n = 3.
^bIn vitro antimalarial activities were calculated against the chloroquine-sensitive 3D7 strain of P. falciparum.
^cSee reference (16).

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