Atovaquone D4

Atovaquone-d₄ is intended for use as an internal standard for the quantification of atovaquone by GC- or LC-MS. Atovaquone is a broad-spectrum antiprotozoal agent that is active against Plasmodium, Toxoplasma, and Babesia, among other protozoa.¹ It inhibits complex III activity on dihydroorotate in isolated P. falciparum and P. yoelii mitochondria more potently than in rat liver mitochondria (EC₅₀s = 0.95, 0.94, and 510 nM, respectively) and depolarizes the mitochondrial membrane in P. yoelii-infected mouse erythrocytes (EC₅₀ = 260 nM).^2,3 Atovaquone also inhibits transport mediated by human breast cancer resistance protein (BCRP) and P-glycoprotein in membrane vesicles (IC₅₀s = 0.23 and 6.8 μM, respectively).⁴ It inhibits the growth of T. gondii in MRC-5 human lung fibroblasts in vitro (IC₅₀ = ~64 nM) and increases mean survival of T. gondii-infected mice from 5.5 to 21.2 days when administered at a dose of 100 mg/kg per day.⁵ Formulations containing atovaquone have been used in the treatment of Pneumocystis pneumonia and toxoplasmosis as well as in combination with proguanil in the treatment of malaria and babesiosis.

1.Kessl, J.J., Lange, B.B., Merbitz-Zahradnik, T., et al.Molecular basis for atovaquone binding to the cytochrome bc1 complexJ. Biol. Chem.278(33)31312-31318(2003) 2.Fry, M., and Pudney, M.Site of action of the antimalarial hydroxynaphthoquinone, 2-[trans-4-(4'-chlorophenyl) cyclohexyl]-3-hydroxy-1,4-naphthoquinone (566C80)Biochem. Pharmacol.43(7)1545-1553(1992) 3.Srivastava, I.K., Rottenberg, H., and Vaidya, A.B.Atovaquone, a broad spectrum antiparasitic drug, collapses mitochondrial membrane potential in a malarial parasiteJ. Biol. Chem.272(7)3961-3966(1997) 4.Rijpma, S.R., van den Heuvel, J.J., van der Velden, M., et al.Atovaquone and quinine anti-malarials inhibit ATP binding cassette transporter activityMalar. J.13359(2014) 5.Romand, S., Pudney, M., and Derouin, F.In vitro and in vivo activities of the hydroxynaphthoquinone atovaquone alone or combined with pyrimethamine, sulfadiazine, clarithromycin, or minocycline against Toxoplasma gondiiAntimicrob. Agents Chemother.37(11)2371-2378(1993)