Cytotoxic C-methylated chalcones from Syzygium samarangense

Abstract

The flavonoids 2′-hydroxy-4′,6′-dimethoxy-3′- methylchalcone (1), 2′,4′-dihydroxy-6′-methoxy-3′, 5′-dimethylchalcone (2), 2′,4′-dihydroxy-6′-methoxy- 3′-methylchalcone (3), 2′,4′-dihydroxy-6′-methoxy- 3′-methyldihydrochalcone (4) and 2′,4′-dihydroxy-6′- methoxy-3′,5′-dimethyldihydrochalcone (5), isolated from Syzygium samarangense (Blume) Merr. & L.M. Perry (Myrtaceae), were subjected to cytotoxicity testing using the dimethylthiazoldiphenyl tetrazolium (MTT) assay. The cell lines used were the Chinese hamster ovarian (CHO-AA8) and the human mammary adenocarcinoma, (MCF-7 and SKBR-3). Among the test compounds, 2 exhibited significant differential cytotoxicity against the MCF-7 cell line with an IC50 of 0.0015 ± 0.0001 nM. It was also cytotoxic against the SKBR-3 cell line with an IC50 of 0.0128 ± 0.0006 nM. Doxorubicin, the positive control, had an IC50 of 2.60 ± 0.28 × 10-4 nM against the MCF-7 cell line and an IC50 of 2.76 ± 0.52 × 10-5 nM against the SKBR-3 cell line. When tested in a mechanism-based yeast bioassay for detecting DNA-damaging agents using genetically engineered Saccharomyces cerevisiae RS322Y (RAD52) mutant strain and (LF15/11) (RAD+) wild-type strain, 2 showed significant selective cytotoxicity against the RAD52 yeast mutant strain. It had an IC12 of 0.1482 nM, as compared with the positive control, streptonigrin, which had an IC12 of 0.0134 nM. Hence, 2 is a cytotoxic natural product with potential anticancer application. © 2007 Informa Healthcare USA, Inc.