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 fractionation of the petroleum ether extract of rhizomes of Amomum aculeatum Roxb. led to the isolation of three novel dioxadispiro5.1.5.2]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‐dioxadispiro5.1.5.2]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‐dioxadispiro5.1.5.2]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 ).