Antiprotozoal Activity and Cytotoxicity of Novel 1,7-Dioxadispiro[5.1.5.2]pentadeca-9,12-dien-11-one Derivatives fromAmomum aculeatum

Abstract

Cytotoxicity against the KB cancer cell line as a lead bioactivity-guided fractionation of the petroleum ether extract of rhizomes of Amomum aculeatum Roxb. led to the isolation of three novel dioxadispiro[5.1.5.2]pentadeca-9,12-dien-11-one derivatives. The structures of aculeatin A (1), aculeatin B (2), and aculeatin C (3) were established as rel-(2R,4R,6S)- and rel-(2R,4R,6R)-4-hydroxy-2-tridecyl-1,7-dioxadispiro[5.1.5.2]pentadeca-9,12-dien-11-one (1 and 2, resp.) and rel-(2R,4R,6R)-2-[4-(3-dodecyl-2-heptyl-3-hydroxy-6-oxocylohexa-1,4-dienyl)-2-oxobutyl]-4-hydroxy-1,7-dioxadispiro[5.1.5.2]pentadeca-9,12-dien-11-one (3) by extensive spectroscopic analyses, particularly 13C-NMR, inverse-gated 13C, HMQC, HMBC, NOESY, and INADEQUATE NMR experiments as well as mass spectrometry. The aculeatins represent a novel type of natural products. All compounds showed high cytotoxicity against the KB cell line: 1, IC50=1.7 μM; 2, IC50=2.0 μM; 3, IC50=1.6 μM. Additional testing against two Plasmodium falciparum strains as well as against trypomastigote forms of Trypanosoma brucei rhodesiense and Trypanosoma cruzi showed strong activities, particularly against P. falciparum strain K1 (1, IC50=0.18 μM; 2, IC50=0.43 μM; 3, IC50=0.37 μM).