Synthesis, antimalarial activity and cytotoxicity of substituted 3,6-diphenyl-[1,2,4,5]tetraoxanes.

Substituted tetraoxanes with different substitution pattern on the aromatic ring were synthesized in order to explore the influence of different substituents in the antimalarial activity. Antimalarial activity of these compounds improves by the introduction of ethyl, iso-propyl or n-propyl groups in the aromatic ring but substitution with n-butyl or t-butyl leads decrease in antimalarial activity. Some of these compounds exhibit promising antimalarial activity. None of the compounds shows any toxicity against vero cells and three compounds (2a-2c) were tested against panel of six cell lines and none of these compounds showed any toxicity. X-ray crystal structure of compound 2w showed that tetraoxane ring is in the chair conformation with both the phenyl rings in the equatorial position. In addition, FeCl(3) mediated O-O bond scission of tetraoxanes (2a-2c) was also examined.