Cytotoxic Lignans and Sesquiterpenoids from the Rhizomes of Acorus tatarinowii

Abstract

Five new compounds, including a rare phenyldihydronaphthalene lignanamide (1), an unusual hybrid-norlignan derivative (2), a rare cycloheptenone oxide derivative (3), one new acorane-type sesquiterpenoid (4), and one new guaiane-type sesquiterpenoid (5), together with seven known compounds (6–12), have been isolated from the rhizomes of Acorus tatarinowii. The structures of compounds 1–5 were determined by means of extensive spectroscopic methods. To the best of our knowledge, this is first report of a phenyldihydronaphthalene lignanamide and hybrid-norlignan and cycloheptenone oxide derivatives from the genus Acorus. In addition, compound 5 represents the first guaiane-type sesquiterpenoid with an epoxy group located between C-6 and C-9 from natural sources. Compounds 1–12 were evaluated for their in vitro cytotoxicity against five tumor cell lines. Among them, 2, 3, 5, and 10 exhibited moderate cytotoxicity with IC₅₀ values of 2.11–9.23 µM.

Key words

Acorus tatarinowii - Araceae - lignan derivative - sesquiterpenoid - cytotoxicity

• References

• 1 Liao WP, Chen L, Yi YH, Sun WW, Gao MM, Su T, Yang SQ. Study of antiepileptic effect of extracts from Acorus tatarinowii Schott. Epilepsia 2005; 46: 21-24
• 2 Zhu MJ, Zhu HZ, Zeng ZG, Chu HB, Wang H, Xia Z, Wu R, Tan NH, Zeng GZ. The effects of Acorus tatarinowii Schott on 5-HT concentrations, TPH2 and 5-HT1B expression in the dorsal raphe of exercised rats. J Ethnopharmacol 2014; 158 Pt A: 431-436
• 3 Hu JF, Feng XZ. Phenylpropanes from Acorus tatarinowii . Planta Med 2000; 66: 662-664
• 4 Tong XG, Wu GS, Huang CG, Lu Q, Wang YH, Long CL, Luo HR, Zhu HJ, Cheng YX. Compounds from Acorus tatarinowii: determination of absolute configuration by quantum computations and cAMP regulation activity. J Nat Prod 2010; 73: 1160-1163
• 5 Ni G, Shen ZF, Lu Y, Wang YH, Tang YB, Chen RY, Hao ZY, Yu DQ. Glucokinase-activating sesquilignans from the rhizomes of Acorus tatarinowii Schott. J Org Chem 2011; 76: 2056-2061
• 6 Wang MF, Lao AN, Wang HC. Two new isopimaranes diterpenes from the roots of Acorus tatarinowii Schott. Chin Chem Lett 1997; 8: 37-38
• 7 Tong XG, Zhou LL, Wang YH, Xia CF, Wang Y, Liang M, Hou FF, Cheng YX. Acortatarins A and B, two novel antioxidative spiroalkaloids with a naturally unusual morpholine motif from Acorus tatarinowii . Org Lett 2010; 12: 1844-1847
• 8 Tong XG, Qiu B, Luo GF, Zhang XF, Cheng YX. Alkaloids and sesquiterpenoids from Acorus tatarinowii . J Asian Nat Prod Res 2010; 12: 438-442
• 9 Wang MF, Lao AN, Wang HC. Two new amides from the roots of Acorus tatarinowii Schott. Chin Chem Lett 1997; 8: 35-36
• 10 Feng XL, Yu Y, Gao H, Mu ZQ, Cheng XR, Zhou WX, Yao XS. New sesquiterpenoids from the rhizomes of Acorus tatarinowii . RSC Adv 2014; 4: 42071-42077
• 11 Rodríguez-Páez L, Juárez-Sanchez M, Antúnez-Solís J, Baeza I, Wong C. Alpha-asarone inhibits HMG-CoA reductase, lowers serum LDL-cholesterol levels and reduces biliary CSI in hypercholesterolemic rats. Phytomedicine 2003; 10: 397-404
• 12 Limón ID, Mendieta A, Díaz A, Chamorro G, Espinosa B, Zenteno E, Guevara J. Neuroprotective effect of alpha-asarone on spatial memory and nitric oxide levels in rats injected with amyloid-β . Neurosci Lett 2009; 453: 98-103
• 13 Momin RA, Nair MG. Pest-managing efficacy of trans-asarone isolated from Daucus carota L. seeds. J Agric Food Chem 2002; 50: 4475-4478
• 14 Cassani-Galindo M, Madrigal-Bujaidar E, Chamorro G, Díaz F, Tamariz J, Espinosa-Aguirre JJ. In vitro genotoxic evaluation of three α-asarone analogues. Toxicol In Vitro 2005; 19: 547-552
• 15 Chamorro G, Salazar M, Salazar S, Mendoza T. Farmacología y toxicología de Guatteria gaumeriy alfa-asarona. Rev Invest Clin 1993; 45: 597-604
• 16 López ML, Hernández A, Chamorro G, Mendoza-Figueroa T. Alpha asarone toxicity in long-term cultures of adult rat hepatocytes. Planta Med 1993; 59: 115-120
• 17 Morales-Ramírez P, Madrigal-Bujaidar E, Mercader-Martínez J, Cassani M, González G, Chamorro-Cevallos G, Salazar-Jacobo M. Sister-chromatid exchange induction produced by in vivo and in vitro exposure to alpha-asarone. Mutat Res 1992; 279: 269-273
• 18 Salazar M, Salazar S, Ulloa V, Mendoza T, Pages N. Action tératogene de lʼ alpha-asarone chez le souris. J Toxicol Clin Exp 1992; 12: 149-154
• 19 Ni G, Yu DQ. [Chemical constituents from rhizomes of Acorus tatarinowii]. Zhongguo Zhong Yao Za Zhi 2013; 38: 569-573
• 20 Zhang F, Qi P, Xue R, Li ZX, Zhu KC, Wan P, Huang CG. Qualitative and quantitative analysis of the major constituents in Acorus tatarinowii Schott by HPLC/ESI-QTOF-MS/MS. Biomed Chromatogr 2015; 29: 890-901
• 21 Jaiswal Y, Liang Z, Ho A, Chen H, Zhao ZZ. Metabolite profiling of tissues of Acorus calamus and Acorus tatarinowii rhizomes by using LMD, UHPLC-QTOF MS, and GC-MS. Planta Med 2015; 81: 333-341
• 22 Yu S, Kim E, Lee J, Lee K, Hong J. Development of fingerprints for quality control of Acorus species by gas chromatography/mass spectrometry. Bull Korean Chem Soc 2011; 32: 1547
• 23 Wang Y, Chang L, Zhao X, Meng X, Liu Y. Gas chromatography-mass spectrometry analysis on compounds in volatile oils extracted from Yuan Zhi (Radix Polygalae) and Shi Chang Pu (Acorus tatarinowii) by supercritical CO₂ . J Tradit Chin Med 2012; 32: 459-464
• 24 Rahman AU, Bhatti MK, Akhtar F, Choudhary MI. Alkaloids of Fumaria indica . Phytochemistry 1992; 31: 2869-2872
• 25 Seca AM, Silva AM, Silvestre AJ, Cavaleiro JA, Domingues FM, Neto C. Lignanamides and other phenolic constituents from the bark of kenaf (Hibiscus cannabinus). Phytochemistry 2001; 58: 1219-1223
• 26 Shimizu M, Hayashi T, Morita N, Kiuchi F, Noguchi H, Iitaka Y, Sankawa U. The structure of paeoniflorigenone, a new monoterpene isolated from Paeoniae radix . Chem Pharm Bull 1983; 31: 577-583
• 27 Skakibara I, Ikeya Y, Hayashi K, Mitsuhashi H. Three phenyldihydronaphthalene lignanamides from fruits of Cannabis sativa . Phytochemistry 1992; 31: 3219-3223
• 28 Ding JY, Yuan CM, Cao MM, Liu WW, Yu C, Zhang HY, Zhang Y, Di YT, He HP, Li SL, Hao XJ. Antimicrobial constituents of the mature carpels of Manglietiastrum sinicum . J Nat Prod 2014; 77: 1800-1805
• 29 Yin HB, He ZS, Ye Y. Cartorimine, a new cycloheptenone oxide derivative from Carthamus tinctorius . J Nat Prod 2000; 63: 1164-1165
• 30 Harada N, Nakanishi K. A method for determining the chiralities of optically active glycols. J Am Chem Soc 1969; 91: 3989-3991
• 31 Nawamaki K, Kuroyanagi M. Sesquiterpenoids from Acorus calamus as germination inhibitors. Phytochemistry 1996; 43: 1175-1182
• 32 Ye XL. Stereochemistry. Beijing: Beijing University Express; 1999: 257-259
• 33 Kuhnke J, Bohlmann F. Enantioselektive Synthese von (−)-Lycoseron und verwandten Verbindungen. Liebigs Ann Chem 1988; 8: 743-748
• 34 Zhang HJ, Tan GT, Santarsiero BD, Mesecar AD, Hung NV, Cuong NM, Soejarto DD, Pezzuto JM, Fong HH. New sesquiterpenes from Litsea verticillata . J Nat Prod 2003; 66: 609-615
• 35 Hao ZY, Liang D, Luo H, Liu YF, Ni G, Zhang QJ, Li L, So YK, Sun H, Chen RY, Yu DQ. Bioactive sesquiterpenoids from the rhizomes of Acorus calamus . J Nat Prod 2012; 75: 1083-1086
• 36 Sun K, Li X, Li W, Wang JH, Liu JM, Sha Y. Two new lactones and one new aryl-8-oxa-bicyclo[3, 2, 1]oct-3-en-2-one from Descurainia Sophia . Chem Pharm Bull 2004; 52: 1483-1486
• 37 Ni G, Zhang QJ, Zheng ZF, Chen RY, Yu DQ. 2-Arylbenzofuran derivatives from Morus cathayana . J Nat Prod 2009; 72: 966-968