Cytotoxic and anti-HIV-1 constituents of Gardenia obtusifolia and their modified compounds

Abstract

5α-Cycloart-24-ene-3,23-dione ( 1 ), 5α-cycloart-24-ene-3,16,23-trione ( 2 ) and methyl 3,4- seco-cycloart-4(28),24-diene-29-hydroxy-23-oxo-3-oate ( 3 ), together with five known flavones 5,7,4′-trihydroxy-3,8-dimethoxyflavone ( 4 ), 5,7,4′-trihydroxy-3,8,3′-tri-methoxyflavone ( 5 ), 5,7,4′-trihydroxy-3,6,8-trimethoxyflavone ( 6 ), 5,4′-dihydroxy-3,6,7,8-tetramethoxyflavone ( 7 ) and 5,3′-dihydroxy-3,6,7,8,4′-pentamethoxyflavone ( 8 ) have been isolated from the leaves and twigs of Gardenia obtusifolia. The structures were assigned on the basis of spectroscopic methods. Compounds 3– 8 and some of the modified compounds showed significant cytotoxic activities in several mammalian cell lines, especially 8 and its diacetate 21 which exhibited potent cytotoxicities (compound 8 : P-388 0.05 μg/mL, KB 0.09 μg/mL, BCA-1 0.63 μg/mL, Lu-1 0.09 μg/mL, ASK 0.70 μg/mL; its diacetate: P-388 0.27 μg/mL, KB 0.06 μg/mL, BCA-1 0.53 μg/mL, Lu-1 0.49 μg/mL). It was also found that 5 , 8 and 21 showed antimitotic acitivity in the ASK assay. Compounds 2 , 4 , 6 , 7 and some of the modified compounds displayed interesting anti-HIV activity in the syncytium assay, but were inactive or exhibited weak activity in the HIV-1 RT assay; while compound 3 was found to be active in the HIV-1 RT assay (99.9 % inhibition at 200 μg/mL), but cytotoxic in the syncytium assay.