New Lignans and Cytotoxic Constituents from Schisandra propinqua

Abstract

The CHCl₃ extract from the stems of Schisandra propinqua (Wall.) Baill exhibited significant cytotoxic activity against cancer cell lines. Subsequent fractionation procedures led to the isolation of four new dibenzocyclooctadiene lignans, propinquanins A - D, along with two known lignans, schisantherin I and heteroclitin A, and three known triterpenoids, isoschisandrolic acid, schisandrolic acid and schisandronic acid. Their structures, including absolute stereochemistry, were elucidated through analyses of NMR data and CD spectra. The isolated compounds were tested for their cytotoxic activity in several tumor cell lines with the MTT assay. Propinquanin B (2) was significantly cytotoxic (IC₅₀ values < 10μM) in HL-60 and Hep-G2 tumor cell lines. Cell cycle analysis and Hoechst 33 258 staining assay suggested that one possible mechanism of cytotoxic activity by 2 might be related to the induction of apoptosis.

Key words

Schisandra propinqua (Wall.) Baill - Schisandraceae - dibenzocyclooctadiene - lignans - triterpenoids - cytotoxictity

References

• 1 Chen Y G, Qin G W, Xie Y Y. Dibenzocyclooctadiene lignans from Schisandra propinqua .  Chem J Chin Univ. 2001;  22 1518-20
• 2 Chen Y G, Qin G W, Xie Y Y. Lignans from Schisandra propinqua (Wall.) Hook. f. et Thoms.  Chin J Chin Mater Med. 2001;  24 105-7
• 3 Chen Y G, Qin G W, Xie Y Y. Studies on chemical constituents of Schisandra propinqua (Wall.) Hook. f. et Thoms.  Chin J Chin Mater Med. 2001;  26 694-7
• 4 Li Z Y, Li L, Zhang H B. Studies on the chemical constituents of Zhongjian wuweizi .  Chin Tradit Herb Drugs. 1996;  27 3-4
• 5 Liu J S, Ma Y T, Huang M F. Studies on the constituents of Schisandraceae plants in Shennongjia District. I. Constituents of Schisandra propinqua Hook. F. et Thoms. var. sinensis Oliv.  Acta Chim Sin. 1988;  46 345-8
• 6 Chen Y G, Qin G W, Xie Y Y. A novel triterpenoid lactone, schiprolactone A, from Schisandra propinqua (Wall.) Hook. f. et Thoms.  Chem J Chin Univ. 2001;  19 304-7
• 7 Chen Y G, Qin G W, Cao L, Leng Y, Xie Y Y. Triterpenoid acids from Schisandra propinqua with cytotoxic effect on rat luteal cells and human decidual cells in vitro .  Fitoterapia. 2001;  72 435-7
• 8 Liu J S, Huang M F, Tao Y. Anwuweizonic acid and manwuweizic acid, the putative anticancer active principle of Schisandra propinqua .  Can J Chem. 1988;  66 414-5
• 9 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.  J Immunol Methods. 1983;  65 55-63
• 10 Liu J S, Ma Y T. Studies on the constituents of Schisandraceae plants in Shennongjia District.III. Isolation and structures of schisantherin G, H and I.  Acta Chim Sin. 1988;  46 465-71
• 11 Chen D F, Xu G J, Yang X W, Hattori M, Tezuka Y, Kikuchi T. et al . Dibenzocyclo-octadiene lignans from Kadsura heteroclita .  Phytochemistry. 1992;  31 629-32
• 12 Sy L K, Richard M K, Brown G D. Phytochemistry of Illicium dunnianum and the systematic position of the Illiciaceae.  Phytochemistry. 1997;  44 1099-108
• 13 Kotaro T, Masako T. Studies on constituents of medicinal plants. XIV. Constituents of Schizandra nigra Max.  Chem Pharm Bull. 1975;  23 537-42
• 14 Chen D F, Zhang S X, Chen K, Zhou B N, Wang P, Cosentino L M. et al . Two new lignans, interiotherins A and B, as anti-HIV principles from Kadsura interior .  J Nat Prod. 1996;  59 1066-8
• 15 Chen Y G, Wang P, Lin Z W, Sun H D, Qin G W, Xie Y Y. Dibenzocyclooctadiene lignans from Kadsura angustifolia .  Phytochemistry. 1998;  48 1059-62
• 16 Liu J S, Ma Y T. Constituents of Schisandraceae plants in Shennongjia District. II. Isolation and structure of schisantherin F.  Acta Chim Sin. 1988;  46 460-4
• 17 Kuo Y H, Li S Y, Huang R L, Wu M D, Huang H C, Lee K H. Schizarin B, C, D and E, four new lignans from Kadsura matsudai and their antihepatitis activities.  J Nat Prod. 2001;  64 487-90
• 18 Ikeya Y, Taguchi H, Yosioka H. The constituents of Schizandra chinensis Baill. I. Isolation and structure determination of five new lignans, gomisin A, B, C, F and G, and the absolute structure of schizandrin.  Chem Pharm Bull. 1979;  27 1383-94