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

Abstract

Cytotoxicity against the KB cancer cell line as a lead bioactivity-guided fractionation of the petroleum ether ext. of rhizomes of Amomum aculeatum RoxB. led to the isolation of three novel dioxadispiro[5.1.5.2]-pentadeca-9,12-dien-11-one derivs. The structures of aculeatin A, aculeatin B, and aculeatin C 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 and rel-(2R,4R,6R)-2-[4-(3-dodecyl-2-heptyl-3-hydroxy-6-oxocyclohexa-1,4-dienyl)-2-oxobutyl]-4-hydroxy-1,7-dioxadispiro[5.1.5.2]pentadeca-9,12-dien-11-one resp. by extensive spectroscopic analyses, particularly 13C-NMR, inverse-gated 13C, HMQC, HMBC, NOESY, and INADEQUATE NMR expts. as well as mass spectrometry. The aculeatins represent a novel type of natural products. All compds. showed high cytotoxicity against the KB cell line: IC50=1.7 micro M; IC50=2.0 micro M; IC50 = 1.6 micro M resp. Addnl. 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 (IC50=0.18micro M; IC50=0.43micro M; IC50=0.37 micro M).