DNA Topoisomerase Inhibitory Activity of Constituents from the Fruits of <i>Illicium verum</i>

Abstract

Three new compounds, a sesquilignan (1) and two glucosylated phenylpropanoids (2, 3), and seven known compounds (4-10), were isolated from the fruits of Illicium verum HOOK. FIL. (Illiciaceae). The structures of 1-3 were determined based on one and two dimensional (1D-and 2D-) NMR data and electronic circular dichroism (ECD) spectra analyses. Compounds 3, 5, 6, and 8-10 exhibited potent inhibitory activities against topoisomerase II with IC 50 values of 54.6, 25.5, 17.9, 12.1, 0.3 and 1.0 µM, respectively, compared to etoposide, the positive control, with an IC 50 of 43.8 µM.Key words Illicium verum; topoisomerase I; topoisomerase II; cytotoxicity Star anise (the fruits of Illicium verum HOOK. FIL., Illiciaceae) has been used as a traditional medicine to treat diverse disease such as stomach aches, insomnia, and skin inflammation in Asia.1,2) Several sesquiterpenoids, flavonoids, phenylpropanoids and lignans have been previously isolated from this plant [3][4][5][6] and been reported to possess anti-human immunodeficiency virus (HIV), cancer chemopreventive and antifungal activities.7-9) The authors previously reported medicinal plant derived compounds that inhibit topoisomerases I and II. [10][11][12][13][14][15] Topoisomerases are enzymes that control DNA topology in cells and are targets of anticancer drugs.16,17) Topoisomerase I cleaves and reseals one DNA strand at a time without requiring ATP to pass the complementary strand through the enzyme-linked strand break, and thus affect DNA relaxation. On the other hand, topoisomerase II cleaves both strands of DNA during catalysis. In a reaction coupled to ATP binding and hydrolysis, these proteins were found to cleave one DNA duplex, transport a second duplex through the break, and then ligate the cleaved duplex. [18][19][20] Camptothecin (CPT) and etoposide (VP-16) are well-known inhibitors of topoisomerases I and II, respectively. 16,17) Here, the authors report the isolation of ten compounds, including a new sesquilignan and two new glycosylated phenylpropanoids, from the fruits of I. verum, and describe cytotoxicity and their DNA topoisomerases I and II inhibitory activities. Results and DiscussionThree new (1-3) and seven known compounds (4-10) were isolated by various chromatographic separations from the EtOAc extract of the fruits of I. verum (Fig. 1). The molecular formula of 1 was established as C 30

Inhibition of DNA Topoisomerases I and II and Cytotoxicity of Compounds from Polygonum aviculare L .

“…Topoisomerase Ι (Topo Ι) and topoisomerase II (Topo II) catalyze the passage of the DNA strand and double strands through a transient single-strand break without any high-energy cofactor and a transitory double-strand break with ATP, respectively [3]. CPT and VP-16 are wellknown Topo Ι and II inhibitors, respectively [4], but their side effects have been reported, known as DNA damage in cancer cells and fast-growing normal cells [5], which highlights the necessity of finding a safer agent of DNA topoisomerase (without or with fewer side effects).…”