Lignans from the bark of Machilus thunbergii and their DNA topoisomerases I and II inhibition and cytotoxicity.
Activity-guided fractionation based on topoisomerase I inhibitory activity lead to the isolation of ten lignans (1-10) from the methylene chloride extract of the bark of Machilus thunbergii SIEB. et ZUCC. (Lauraceae). These were identified as machilin A (1), erythro-austrobailignan-6 (2), meso-monomethyl dihydroguaiaretic acid (3), meso-dihydroguaiaretic acid (4), galbacin (5), machilin F (6), nectandrin A (7) nectandrin B (8), (-)-acuminatin (9) and (7S,8S)-7-(4-hydroxy-3-methoxyphenyl)-1'-formyl-3'-methoxy-8-methyldihydrobenzofuran (10) by spectral evidence. In DNA topoisomerase I and II assays in vitro at a concentration of 100 microM, 4 showed the most potent inhibitory activity, 93.6 and 82.1% inhibition, respectively, and 8 showed 79.1 and 34.3% inhibition, respectively. All of these compounds exhibited weak or no cytotoxicities against either the human colon carcinoma cell line (HT-29) or the human breast carcinoma cell line (MCF-7).
Li
Gao
G
College of Pharmacy, Yeungnam University, Gyongsan, Korea.
Lee
Chong-Soon
CS
Woo
Mi-Hee
MH
Lee
Seung-Ho
SH
Chang
Hyeun-Wook
HW
Son
Jong-Keun
JK
D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity*; D019073:HT29 Cells; D006801:Humans; D019770:Lauraceae; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity*; D024301:Plant Bark; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D004791:Enzyme Inhibitors; D017705:Lignans; D010936:Plant Extracts; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II