New Indolopyridoquinazoline, Benzo[c]phenanthridines and Cytotoxic Constituents from Zanthoxylum integrifoliolum

Abstract

Three new alkaloids, 7,8-dehydro-1-methoxyrutaecarpine, isodecarine, and 8-demethyloxychelerythrine, together with sixteen known compounds, norchelerythrine, oxychelerythrine, decarine, dihydrocherythrinylacetaldehyde, 6-acetonyldihydrochelerythrine, rutaecarpine, 1-hydroxyrutaecarpine, γ-fagarine, skimmianine, (-)-matairesinol, (-)-isoarctigenin, (+)-epipinoresinol, d-sesamin, lupeol, canthin-6-one, and arnottianamide have been isolated from the root bark of Zanthoxylum integrifoliolum. The structures of these new compounds were determined through spectral analyses. Among the isolates, 7,8-dehydro-1-methoxyrutaecarpine, norchelerythrine, oxychelerythrine, dihydrocherythrinylacetaldehyde, 6-acetonyldihydrochelerythrine, 1-hydroxyrutaecarpine, γ-fagarine, skimmianine, (-)-matairesinol, and canthin-6-one exhibited cytotoxicities (ED₅₀ values < 4 μg/mL) against P-388 or HT-29 cell lines in vitro.

Key words

Zanthoxylum integrifoliolum - Rutaceae - root bark - 7,8-dehydro-1-methoxyrutaecarpine - isodecarine - 8-demethyloxychelerythrine - cytotoxicity

References

• 1 Chang C E, Hartley T G. Rutaceae in Flora of Taiwan. 2nd edition. Editorial Committee of the Flora of Taiwan Taipei, Taiwan; 1993 Vol. 3: 510-44
• 2 Ko F N, Hsiao G, Chen I S, Wu S J, Teng C M. Inhibition of collagen-induced platelet aggregation and adhesion by a pseudocyanide derivative of avicine isolated from Zanthoxylum integrifoliolum Merr.  Biochem Pharmacol. 1993;  46 1165-73
• 3 Tsai I L, Lin W Y, Huang M W, Chen T L, Chen I S. N-Isobutylamides and butyrolactone from the fruits of Zanthoxylum integrifoliolum .  Helv Chim Acta. 2001;  84 830-3
• 4 Chen I S, Chen T L, Lin W Y, Tsai I L, Chen Y C. Isobutylamides from the fruit of Zanthoxylum integrifoliolum .  Phytochemistry. 1999;  52 357-60
• 5 Chen I S, Chen T L, Chang Y L, Teng C M, Lin W Y. Chemical constituents and biological activities of the fruit of Zanthoxylum integrifoliolum .  J Nat Prod. 1999;  62 833-7
• 6 Liu S L, Tsai I L, Ishikawa T, Harayama T, Chen I S. Bishordeninyl terpene alkaloids from Zanthoxylum integrifoliolum .  J Chin Chem Soc. 2000;  47 571-4
• 7 Ishii H, Chen I S, Akaike M, Ishikawa T, Lu S T. Studies on the chemical constituents of Rutaceous plants. XLIV. The chemical constituents of Xanthoxylum integrifoliolum (Merr.) Merr. (Fagara integrifoliola Merr.) (1) The chemical constituents of the root wood.  Yakugaku Zasshi. 1982;  102 182-95
• 8 Jen C M, Tsai I L, Horng D J, Chen I S. Isolation and structure determination of two new compounds from Zanthoxylum integrifoliolum .  J Nat Prod. 1993;  56 2019-21
• 9 Sheen W S, Tsai I L, Teng C M, Ko F N, Chen I S. Indolopyridoquinazoline alkaloids with antiplatelet aggregation activity from Zanthoxylum integrifoliolum .  Planta Medica. 1996;  62 175-6
• 10 Liu S L, Tsai I L, Ishikawa T, Harayama T, Chen I S. Bishordeninyl terpene alkaloids from Zanthoxylum integrifoliolum .  J Chin Chem Soc. 2000;  47 571-4
• 11 Chaaib F, Queiroz E F, Ndjoko K, Diallo D, Hostettmann K. Antifungal and antioxidant compounds from the root bark of Fagara zanthoxyloides .  Planta Medica. 2003;  69 316-20
• 12 Gozler B, Arar G, Gozler T, Hesse M. Isodaurinol, an arylnaphthalene lignan from Haplophyllum cappadocicum .  Phytochemistry. 1992;  31 2473-5
• 13 Sibi M P, Liu P, Ji J, Hajra S, Chen J -X. Free-radical-mediated conjugate additions. Enantioselective synthesis of butyrolactone natural products: (-)-enterolactone, (-)-arctigenin, (-)-isoarctigenin, (-)-nephrosteranic acid, and (-)-roccellaric acid.  J Org Chem. 2002;  67 1738-45
• 14 Nishibe S, Tsukamoto H, Hisada S. Effects of O-methylation and O-glucosylation on carbon-13 nuclear magnetic resonance chemical shifts of matairesinol, (+)-pinoresinol and (+)-epipinoresinol. Chem. Pharm.  Bull.. 1984;  32 4653-7
• 15 Banerji A, Sarkar M, Datta R, Sengupta P, Abraham K. Amides from Piper brachystachyum and Piper retrofractum .  Phytochemistry. 2002;  59 897-901
• 16 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.  J Immunol Meth. 1983;  65 55-63
• 17 Ikuta A, Nakamura T, Urabe H. Indolopyridoquinazoline, furoquinoline and canthinone type alkaloids from Phellodendron amurense callus tissues.  Phytochemistry. 1998;  48 285-91
• 18 Geen G R, Mann I S, Mullane M V, McKillop A. A versatile synthesis of fully aromatic benzo[c]phenanthridine alkaloids.  Tetrahedron. 1998;  54 9875-94
• 19 Tolkachev O N, Savina A A, Sheichenko V I, Proskudina V V. On the mechanism of thermolysis of the benzo[c]phenanthridine alkaloid chelerythrine.  Pharm Chem J. 1999;  33 323-5
• 20 Hanaoka M, Motonishi T, Mukai C. Chemical transformation of protoberberines. Part 9. A biomimetic synthesis of oxychelerythrine, dihydrochelerythrine, and chelerythrine from berberine. J Chem Soc Perkin Trans 1 1986: 2253-6
• 21 Ishikawa T, Takami A, Abe M, Chen I S, Harayama T, Ishii H. Concise synthesis of the oxo derivatives of benzo[c]phenanthridine bases by N-deformylated cyclization based on Vilsmeier-Haack Reaction.  Chem Pharm Bull. 1995;  43 766-70
• 22 Chen I S, Tsai I W, Teng C M, Chen J J, Chang Y L, Ko F N, Lu M C, Pezzuto J M. Pyranoquinoline alkaloids from Zanthoxylum simulans .  Phytochemistry. 1997;  46 525-9
• 23 Decaudain N, Kunesch N, Poisson J. Alcaloïdes de Zanthoxylum tsihanimposa .  Phytochemistry. 1974;  13 505-7
• 24 Chen I S, Lin Y C, Tsai I L, Teng C M, Ko F N, Ishikawa T, Ishii H. Coumarins and anti-platelet aggregation constituents from Zanthoxylum schinifolium .  Phytochemistry. 1995;  39 1091-7
• 25 Rahman M MA, Dewick P M, Jackson D E, Lucas J A. Lignans of Forsythia intermedia .  Phytochemistry. 1990;  29 1971-80
• 26 Cain M, Campos O, Guzman F, Cook J M. Selenium dioxide oxidations in the indole area. Synthesis of β-carboline alkaloids.  J Am Chem Soc. 1983;  105 907-13
• 27 Geran R I, Greenberg N H, Macdonald M M, Schumacher A M, Abbott B J. Protocols for screening chemical agents and natural products against animal tumors and other biological systems.  Cancer Chemother Rep, Part 3. 1972;  3 103