Medicinal Chemistry Research

, Volume 21, Issue 6, pp 722–725 | Cite as

Skimmianine, a furoquinoline alkaloid from Zanthoxylum nitidum as a potential acetylcholinesterase inhibitor

  • Zhong-duo Yang
  • Dong-bo Zhang
  • Jin Ren
  • Ming-jun Yang
Original Research

Abstract

Skimmianine (1), a newly discovered strong acetylcholinesterase (AChE) inhibitor, along with nine weakly or no active compounds, toddalolactone (2), dictamnine (3), γ-fagarine (4), magnolone (5), (−)-(S)-edulinine (6), zanthodioline (7), edulitine (8), 5,6,7-trimethoxycoumarin (9), and haplopine (10) have been isolated from Zanthoxylum nitidum (Z. nitidum). Skimmianine (1) inhibited 50% of AChE activity at the concentrations of 8.6 ± 0.7 μg/ml when the IC50 value of Physostigmine as a standard was 0.013 ± 0.002 μg/ml. Antiacetylcholinesterase activity of skimmianine (1) was also supported by TLC bioautographic assay. The structure activity relationship on the anti-acetylcholinesterase activity of the quinoline moiety is also discussed in this article.

Keywords

Zanthoxylum nitidum Skimmianine Acetylcholinesterase inhibitor Quinoline alkaloid Alzheimer’s disease 

References

  1. Ambrozin ARP, Mafezoli J, Vieira PC, Fernandes JB, da Silva M, Ellena JA, de Albuquerque S (2005) New pyrone and quinoline alkaloid from Almeidea rubra and their trypanocidal activity. J Braz Chem Soc 16:434–439CrossRefGoogle Scholar
  2. Boyd DR, Sharma ND, Barr SA, Carroll JG, Mackerracher D, Malone JF (2000) Synthesis and absolute stereochemistry assignment of enantiopure dihydrofuro- and dihydropyrano-quinoline alkaloids. J Chem Soc Perkin 1(1):3397–3405CrossRefGoogle Scholar
  3. Carpinella MC, Andrione DG, Ruiz G, Palacios SM (2010) Screening for acetylcholinesterase inhibitory activity in plant extracts from Argentina. Phytother Res 24:259–263PubMedGoogle Scholar
  4. Chakravarty AK, Sarkar T, Masuda K, Shiojima K (1999) Carbazole alkaloids from roots of Glycosmis arborea. Phytochemistry 50:1263–1266CrossRefGoogle Scholar
  5. Chaturvedula VSP, Schilling JK, Miller JS, Andriantsiferana R, Rasamison VE, Kingston DGI (2003) New cytotoxic alkaloids from the wood of Vepris punctata from the Madagascar rainforest. J Nat Prod 66:532–534CrossRefGoogle Scholar
  6. Chen IS, Tsai IW, Teng CM, Chen JJ, Chang YL, Ko FN, Lu MC, Pezzuto JM (1997) Pyranoquinoline alkaloids from Zanthoxylum simulans. Phytochemistry 46:525–529CrossRefGoogle Scholar
  7. Chen KS, Chang YL, Teng CM, Chen CF, Wu YC (2000) Furoquinolines with antiplatelet aggregation activity from leaves of Melicope confusa. Planta Med 66:80–81PubMedGoogle Scholar
  8. Cheng JT (1986) Effect of skimmianine on animal behavior. Arch Int Pharmacodyn Ther 281:35–43PubMedGoogle Scholar
  9. Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95PubMedCrossRefGoogle Scholar
  10. Fang SD, Wang LK, Hecht SM (1993) Inhibitors of DNA topoisomerase-I isolated from the roots of Zanthoxylum-nitidum. J Org Chem 58:5025–5027CrossRefGoogle Scholar
  11. Houghton PJ, Ren YH, Howes MJ (2006) Acetylcholinesterase inhibitors from plants and fungi. Nat Prod Rep 23:181–199PubMedCrossRefGoogle Scholar
  12. Hu J, Xu XK, Liu RH, Zhang C, Li HL, Liang MJ, Zhang WD (2006a) Study on lignans constituents of Zanthoxylum nitidum. Pharmaceut Care Res 6:51–53Google Scholar
  13. Hu J, Zhang WD, Liu RH, Zhang C, Shen YH, Li HL, Liang MJ, Xu XK (2006b) Benzophenanthridine alkaloids from Zanthoxylum nitidum (Roxb.) DC, and their analgesic and anti-inflammatory activities. Chem Biodivers 3:990–995PubMedCrossRefGoogle Scholar
  14. Imai F, Itoh K, Kishibuchi N, Kinoshita T, Sankawa U (1989) Constituents of the root bark of Murraya-paniculata collected in Indonesia. Chem Pharm Bull 37:119–123CrossRefGoogle Scholar
  15. Lahiri DK, Farlow MR, Greig NH, Sambamurti K (2002) Current drug targets for alzheimer’s disease treatment. Drug Dev Res 56:267–281CrossRefGoogle Scholar
  16. Li X, Tang HZ, Gou XJ, Tu J (2008) Study on chemical constituents of the root of Dictamnus dasycarpus. Zhong Yao Cai 31:1816–1819Google Scholar
  17. Munoz-Torrero D, Camps P (2006) Dimeric and hybrid anti-alzheimer drug candidates. Curr Med Chem 13:399–422PubMedCrossRefGoogle Scholar
  18. Pang YP, Quiram P, Jelacic T, Hong F, Brimijoin S (1996) Highly potent, selective, and low cost bis-tetrahydroaminacrine inhibitors of acetylcholinesterase—steps toward novel drugs for treating alzheimer’s disease. J Biol Chem 271:23646–23649PubMedCrossRefGoogle Scholar
  19. Rahman AU, Khalid A, Sultana N, Ghayur MN, Mesaik MA, Khan MR, Gilani AH, Choudhary I (2006) New natural cholinesterase inhibiting and calcium channel blocking quinoline alkaloids. J Enzyme Inhib Med Chem 21:703–710CrossRefGoogle Scholar
  20. Snider BB, Wu XX (2006) Synthesis of (+)-myrtopsine, (+)-7,8-dimethoxymyrtopsine, and related 2,3-dihydro-3-hydroxy-2-(1-hydroxy-1-methylethyl) benzofuran natural products. Heterocycles 70:279–294CrossRefGoogle Scholar
  21. Tang J, Zhu W, Tu ZB (1995) Study on chemical constituents of the stem of Zanthoxylum dissitum. Zhong Cao Yao 26:563–565Google Scholar
  22. Wan H-C, Hu D-Y, Liu H-C (2005) Clinical observation of toothpaste containing Zanthoxylum nitidum extract on dental plaque and gingivitis. Zhongguo Zhong Xi Yi Jie He Za Zhi 25:1024–1026PubMedGoogle Scholar
  23. Wang B-L, Liu H-G, Yang B, Qin S-H (2007) Anticancer activity of nitidine chloride from Zanthoxylum nitidum (Roxb.) DC. On multidrug resistant KBV200 cells in vitro. Chin J Pharmacol Toxicol 21:512–515Google Scholar
  24. Yang GH, Chen DF (2008) Alkaloids from the roots of Zanthoxylum nitidum and their antiviral and antifungal effects. Chem Biodivers 5:1718–1722PubMedCrossRefGoogle Scholar
  25. Yang CH, Cheng MJ, Lee SJZ, Yang CWZ, Chang HS, Chen IS (2008) Secondary metabolites and cytotoxic activities from the stem bark of Zanthoxylum nitidum. Planta Med 74:1046Google Scholar
  26. Yang ZD, Zhang X, Duan DZ, Song ZW, Yang MJ, Li S (2009) Modified tlc bioautographic method for screening acetylcholinesterase inhibitors from plant extracts. J Sep Sci 32:3257–3259PubMedCrossRefGoogle Scholar
  27. Ye JH, Zhou YL, Huang ZH (1989) Study on the chemical-constituents of Alstonia-mairei. Acta Chimi Sin 47:1012–1016Google Scholar
  28. Yu HJ, Chen CC, Shieh BJ (1998) Two new constituents from the leaves of Magnolia coco. J Nat Prod 61:1017–1019PubMedCrossRefGoogle Scholar
  29. Zeng XY, Chen XF, He XQ, Hong GX (1982) Studies on the antispasmodic and analgesic actions of crystal-8 isolated from Zanthoxylum nitidum (Roxb.) DC. Yao Xue Xue Bao 17:253–258PubMedGoogle Scholar
  30. Zheng XL, Xing FW (2009) Ethnobotanical study on medicinal plants around mt.Yinggeling, Hainan Island, China. J Ethnopharmacol 124:197–210PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Zhong-duo Yang
    • 1
  • Dong-bo Zhang
    • 1
  • Jin Ren
    • 1
  • Ming-jun Yang
    • 1
  1. 1.School of Life Science and EngineeringLanzhou University of TechnologyLanzhouPeople’s Republic of China

Personalised recommendations