Cytotoxic Homoisoflavones from the Bulbs of Bellevalia eigii

Abstract

Eight new and 10 known compounds were isolated from an organic extract of the bulbs of Bellevalia eigii as part of a search for anticancer leads from native plants of Jordan. Of these, the series of 16 homoisoflavonoids (1-16) comprise the seven new analogues 7-O-methyl-3'-hydroxy-3,9-dihydropunctatin (3), 6-hydroxy-7-O-methyl-3,9-dihydropunctatin (6), 7,4'-di-O-methyl-3'-hydroxy-3,9-dihydropunctatin (9), 7-O-methylpunctatin (10), 7-O-methyl-3'-hydroxypunctatin (13), 5-hydroxy-7,8-dimethoxychroman-4-one (14), and 7-O-methyl-8-demethoxy-3-hydroxy-3,9-dihydropunctatin (15). The known ferulic acid-derived acrylamide (17) and the new methylthioacrylate bellegimycin (18) are also reported. The structures were elucidated using a set of spectroscopic and spectrometric techniques; the absolute configurations of compounds 1-9, 15, and 16 were determined using ECD spectroscopy, while a modified Mosher's ester method was used for compound 18. Optical rotation data for the known compounds 1, 2, and 8 are reported here for the first time. The cytotoxic activities of all compounds were evaluated using the MDA-MB-435 (melanoma) and HT-29 (colon) cancer cell lines. Compounds 4 and 9 were the most potent on the latter cell line, with IC50 values of 1.0 and 1.1 μM, respectively. Compounds 1-18 were assessed for antimicrobial activity using a collection of bacteria and fungi; compounds 4 and 12 showed promising activity against the bacterium Mycobacterium smegmatis with MIC values of 17 and 24 μg/mL, respectively.

Figure 1

Key COSY and HMBC correlations of 3, 6, 9, 10, 13–15, and 18.

Figure 2

ECD spectra for A) (3) [0.09 mM, MeOH, cell length 2 cm], B) (6) [0.09 mM, MeOH, cell length 2 cm], C) (9) [0.08 mM, MeOH, cell length 2 cm], and D) (15) [0.09 mM, MeOH, cell length 2 cm].

Figure 3

Δδ_H values [Δδ (in ppm) = δ_S – δ_R] obtained for (S)– and (R)–MTPA esters 18a and 18b, respectively of bellegimycin (18) in pyridine–d₅.