Abstract
A series of diterpene alkaloid derivatives (1–6) are prepared by reaction of the lappaconitine (0) with the corresponding organic or inorganic acid. The lappaconitine was isolated from the root of Aconitum sinomontanum Nakai in Gansu Province in China. The structures of all newly synthesized compounds were established by analytical and spectral data. In particular, the configurations of compounds 0–3 were determined by X-ray single-crystal diffraction. The analgesic potential has been investigated. Among the compounds tested, all derivatives (1–6) produced antinociceptive effects in a mouse model of acute pain, without inducing undesirable side effects. Furthermore, lappaconitine sulphate exhibited a pronounced analgesic activity. Thus, the present findings have demonstrated that lappaconitine sulphate is a promising analgesic agent and could emerge as a promising analgesic agent for further research work.
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References
Ahmad M, Ahmad W, Ahmad M, Zeeshan M, Shaheen F (2008) Norditerpenoid alkaloids from the roots of Aconitum heterophyllum Wall with antibacterial activity. J Enzyme Inhib Med Chem 23(6):1018–1022
Birnbaum GI (1970) The crystal and molecular structure of lappaconine hydrobromide. Acta Crystallogr Sect B Struct Crystallogr Cryst Chem 26(6):755–765
De-Quan Y, Das BC (1983) Alkaloids of Aconitum barbatum. Planta Med 49:85–89
Dzhakhangirov FN, Kasymova KR, Sultankhodzhaev MN (2007) Toxicity and local anesthetic activity of diterpenoid alkaloids. Chem Nat Compd 43:581–589
Mu ZQ, Gao H, Huang ZY (2012) Puberunine and puberudine, two new C-18-diterpenoid alkaloids from Aconitum barbatum var. puberulum. Org Lett 14:2758–2761
Negus SS, Vanderah TW, Brandt MR, Bilsky EJ, Becerra L, Borsook D (2006) Preclinical assessment of candidate analgesic drugs: recent advances and future challenges. J Pharmacol Exp Ther 319:507–514
Ou S, Zhao YD, Xiao Z (2011) Effect of lappaconitine on neuropathic pain mediated by P2X(3) receptor in rat dorsal root ganglion. Neurochem Int 58:564–573
Shafikova EU, Tsyrlina EM, Spirikhin LV (2008) Oxidative transformations of lappaconitine and 19-oxolappaconine, structural revision of an obtained 8, 9-seco product. Nat Prod Commun 3(10):1565–1568
Sun LM, Huang HL, Li WH (2009a) Alkaloids from Aconitum barbatum var. puberulum. Helv Chim Acta 92:1126–1133
Sun LM, Nan ZD, Huang HL (2009b) Chemical constituents of Aconitum Barbatum Var. Puberulum. Chem Nat Compd 45:934–935
Sun WX, Wang YP, Zhang J (2009c) X-ray structure analysis of lappaconitine. Nat Prod Res 23:960–962
Sun WX, Yuan AA, Zhang CY, Dong TG (2011a) Crystal structure of acontine-4, 8, 9-triol-19-ethyl-1,14,16-trimethoxy-4-[2-(acetylamino) benzoate] adulterated copper chloride C32H45N2O8Cl2Cu. Adv Mater Res 236:2242–2245
Sun WX, Hu QL, Ding CM, Duan Y, Jia J (2011b) Crystal structure of 2-acetamido-5-bromobenzoic acid, C9H8BrNO3. New Cryst Struct 226(1):75–76
Sun WX, Dong TG, Ding CM (2012) Crystal structure analysis and antinociceptive property of lappaconitine hydrochloride. Adv Mater Res 343:1049–1052
Sun WX, Wang H, Zhang S, Wang X (2014) Crystal structure of lappaconitine-ium nitrate monohydrate, C32H47N3O12. New Cryst Struct 229(4):485–487
Tolstikova TG, Bryzgalov AO, Sorokina IV (2007) Formation of salts with hydrobromic acid determines the antiarrhythmic effect of lappaconitine derivatives. Dokl Biol Sci 415:265–266
Tolstikova TG, Bryzgalov AO, Sorokina IV (2009) Solification with hydrobromic acid as a factor defining the antiarrhythmic effect of lappaconitine derivatives. Lett Drug Des Discovery 6:475–477
Turabekova MA, Rasulev BF, Levkovich MG (2008) Aconitum and delphinium sp alkaloids as antagonist modulators of voltage-gated Na+ channels—AM1/DFT electronic structure investigations and QSAR studies. Comput Biol Chem 32:88–101
Turdybekov DM, Turdybekov KM, Burdel’naya EV, Turmukhambetov AZ, Adekenov SM, Gatilov YV (2003) Crystal structure of lappaconitine hydrobromide hydrate. Chem Nat Compd 39(1):19–21
Wang YP, Sun WX, Zhang J (2007) Lappaconitine. Acta Crystallogr Sect E: Struct Rep Online 63(4):o1645–o1647
Wang JL, Shen XL, Chen QH (2009a) Structure-analgesic activity relationship studies on the C-18- and C-19-diterpenoid alkaloids. Chem Pharm Bull 57:801–807
Wang YZ, Xiao YQ, Zhang C (2009b) Study of analgesic and anti-inflammatory effects of lappaconitine gelata. J Tradit Chin Med 29:141–145
Yunusov MS (2011) Antiarrhythmic agents based on diterpenoid alkaloids. Chem Bull 60:633–638
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This work was financially supported by the Natural Science Fund of Inner Mongolia (No. 2011BS1203) and the Doctoral Fund of Inner Mongolia Agricultural University.
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Sun, W., Zhang, S., Wang, H. et al. Synthesis, characterization and antinociceptive properties of the lappaconitine salts. Med Chem Res 24, 3474–3482 (2015). https://doi.org/10.1007/s00044-015-1402-0
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DOI: https://doi.org/10.1007/s00044-015-1402-0