Antiprotozoal activity and cytotoxicity of novel 1,7-dioxadispiro[5.1.5.2]pentadeca-9,12-dien-11-one derivatives from Amomum aculeatum

Cytotoxicity against the KB cancer cell line as a lead bioactivity-guided f ractionation 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-o ne (1 and 2, resp.) and rel-(2R,4R,6S)-2-[4-(3-dodecyl-2-heptyl-3-hydroxy-6 -oxocylohexa-1,4-dienyl)-2-oxobutyl]-4-hydroxy-1,7-dioxadispiro[5.1.5.2]pen tadeca-9,12-dien-11-one (3) by extensive spectroscopic analyses, particular ly C-13 NMR, inverse-gated C-13, HMQC, HMBC, NOESY, and INADEQUATE NMR expe riments 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 muM; 2, IC50 = 2.0 muM; 3, IC50 = 1.6 muM. Additi onal testing against two Plasmodium falciparum strains as well as against t rypomastigote forms of Trypanosoma brucei rhodesiense and Trypanosoma cruzi showed strong activities, particularly against P. falciparum strain K1 (1, IC50 = 0.18 muM; 2, IC50 = 0.43 muM; 3, IC50 = 0 37 muM).