Meroterpenoids and a Naphthoquinone from Arnebia euchroma and Their Cytotoxic Activity

Abstract

Four new meroterpenoids, arnebinols A–D (1–4), and one new prenylated naphthoquinone, 5,8-O-dimethyl-11-deoxyalkannin (5), together with seven known meroterpenoids (6–12) were isolated from the roots of Arnebia euchroma. The structures of the isolated compounds were elucidated unambiguously by spectroscopic data analysis, as well as X-ray-single crystal diffraction analysis. Arnebinol A (1) and B (2) are rare meroterpenoids possessing a 6/10/5 tricyclic ring system. Compounds 1–12 were evaluated for their cytotoxicities against MG-63 and SNU387 human cancer cell lines. Compound 5 exhibited the most potent activity with IC₅₀ values of 2.69 µM and 6.08 µM, respectively.

Key words

Arnebia euchroma - Boraginaceae - meroterpenoids - arnebinol - cytotoxicity

• References

• 1 Bhatia A, Arora S, Singh B, Kaur G, Nagpal A. Anticancer potential of Himalayan plants. Phytochem Rev 2011; 10: 309-323
• 2 State Pharmacopoeia Committee. Chinese Pharmacopoeia, 2010 edition. Beijing: China Medical Pharmaceutical Science and Technology Publishing House; 2010: 320
• 3 Huang ZS, Zhang M, Ma L, Gu LQ. Chemical and pharmacological research progress of Chinese drug “Zicao”. Nat Prod Res Dev 1999; 12: 73-82
• 4 Papageorgiou VP, Assimopoulou AN, Couladouros EA, Hepworth D, Nicolaou KC. The chemistry and biology of alkannin, shikonin, and related naphthazarin natural products. Angew Chem Int Ed 1999; 38: 270-300
• 5 Shen CC, Syu WJ, Li SY, Lin CH, Lee GH, Sun CM. Antimicrobial activities of naphthazarins from Arnebia euchroma . J Nat Prod 2002; 65: 1857-1862
• 6 Damianakos H, Kretschmer N, Syklowska-Baranek K, Pietrosiuk A, Bauer R, Chinou I. Antimicrobial and cytotoxic isohexenylnaphthazarins from Arnebia euchroma (Royle) Jonst. (Boraginaceae) callus and cell suspension culture. Molecules 2012; 17: 14310-14322
• 7 Kashiwada Y, Nishizawa M, Yamagishi T, Tanaka T, Nonaka G, Cosentino LM, Snider JV, Lee KH. Anti-AIDS agents, 18. Sodium and potassium salts of caffeic acid tetramers from Arnebia euchroma as anti-HIV agents. J Nat Prod 1995; 58: 392-400
• 8 Kashiwada Y, Bastow KF, Lee KH. Novel lignan derivatives as selective inhibitors of DNA topoisomerase II. Bioorg Med Chem Lett 1995; 5: 905-908
• 9 Roeder E, Rengel-Mayer B. Pyrrolizidine alkaloids from Lithospermum erythrorhizon . Phytochemistry 1990; 29: 690-693
• 10 Roeder E, Rengel-Mayer B. Pyrrolizidine alkaloids from Arnebia euchroma . Planta Med 1993; 59: 192
• 11 Yao XS, Ebizuka Y, Noguchi H, Kiuchi F, Sankawa U, Seto H. Structure of arnebinone, a novel monoterpenylbenzoquinone with inhibitory effect to prostaglandin biosynthesis. Tetrahedron Lett 1983; 24: 3247-3250
• 12 Yao XS, Ebizuka Y, Noguchi H, Kiuchi F, Iitaka Y, Sankawa U, Seto H. Structure of arnebinol, a new ansa-type monoterpenylbenzenoid with inhibitory effect to prostaglandin biosynthesis. Tetrahedron Lett 1983; 24: 2407-2410
• 13 Yao XS, Ebizuka Y, Noguchi H, Kiuchi F, Seto H, Sankawa U. Structure of arnebifuranone, new monoterpenylbenzoquine from Arnebia euchroma . Tetrahedron Lett 1984; 25: 5541-5542
• 14 Li HM, Tang YL, Zhang ZH, Liu CJ, Li HZ, Li RT, Xia XS. Compounds from Arnebia euchroma and their related anti-HCV and antibacterial activities. Planta Med 2012; 78: 39-45
• 15 Justicia J, Oltra JE, Cuerva JM. General approach to polycyclic meroterpenoids based on stille couplings and titanocene catalysis. J Org Chem 2004; 69: 5803-5806
• 16 Geris R, Simpson TJ. Meroterpenoids produced by fungi. Nat Prod Rep 2009; 26: 1063-1094
• 17 Yin X, Feng T, Li ZH, Dong ZJ, Li Y, Liu JK. Highly oxygenated meroterpenoids from fruiting bodies of the mushroom Tricholoma terreum . J Nat Prod 2013; 76: 1365-1368
• 18 Reyes CDL, Zbakh H, Motilva V, Zubia E. Antioxidant and anti-inflammatory meroterpenoids from the brown alga Cystoseira usneoides . J Nat Prod 2013; 76: 621-629
• 19 Fadli M, Aracil JM, Jeanty G, Banaigs B, Francisco C. Novel meroterpenoids from Cystoseira mediterranea: use of the crown-gall bioassay as a primary screen for lipophilic antineoplastic agents. J Nat Prod 1991; 54: 261-264
• 20 Fenical W, Sims JJ, Squatrit D, Wing RM, Radlick P. Zonarol and isozonarol, fungitoxic hydroquinones from the brown seaweed Dictyopteris aonarioides . J Org Chem 1973; 38: 2383-2386
• 21 Kaysser L, Bernhardt P, Nam SJ, Loesgen S, Ruby JG, Skewes-Cox P, Jensen PR, Fenical W, Moore BS. Merochlorins A−D, cyclic meroterpenoid antibiotics biosynthesized in divergent pathways with vanadium-dependent chloroperoxidases. J Am Chem Soc 2012; 134: 11988-11991
• 22 Sontag B, Arnold N, Steglich W, Anke T. Montadial A, a cytotoxic metabolite from Bondarzewia montana . J Nat Prod 1999; 62: 1425-1426
• 23 Arnone A, Cardillo R, Meille SV, Nasini G, Tolazzi M. Secondary mould metabolites. 47. Isolation and structure elucidation of clavilactones A–C, new metabolites from the fungus Clitocybe clavipes . J Chem Soc Perkin Trans I 1994; 2165-2168
• 24 Simon-Levert A, Arrault A, Bontemps-Subielos N, Canal C, Banaigs B. Meroterpenes from the ascidian Aplidium aff. densum . J Nat Prod 2005; 68: 1412-1415
• 25 Cassinelli G, Lanzi C, Pensa T, Gambetta RA, Nasini G, Cuccuru G, Cassinis M, Pratesi G, Polizzi D, Tortoreto M, Zunino F. Clavilactones, a novel class of tyrosine kinase inhibitors of fungal origin. Biochem Pharmacol 2000; 59: 1539-1547
• 26 Larrosa I, Da Silva MI, Gómez PM, Hannen P, Ko E, Lenger SR, Linke SR, White AJP, Wilton D, Barrett AGM. Highly convergent three component benzyne coupling: the total synthesis of ent-clavilactone B. J Am Chem Soc 2006; 128: 14042-14043
• 27 Takao K, Nanamiya R, Fukushima Y, Namba A, Yoshida K, Tadano K. Total synthesis of (+)-clavilactone A and (−)-clavilactone B by ring-opening/ring-closing metathesis. Org Lett 2013; 15: 5582-5585
• 28 Lv L, Shen B, Li Z. Total synthesis of (±)-clavilactones A, B, and proposed D through iron-catalyzed carbonylation–peroxidation of olefin. Angew Chem Int Ed Engl 2014; 53: 4164-4167
• 29 Moir M, Thomson RH. Naturally occurring quinones. Part XXIII. Cordiachromes from Patagonula americana L. J Chem Soc Perkin I 1973; 1556-1561
• 30 Moir M, Thomson RH. Naturally occurring quinones. Part XXII. Terpenoid quinones in Cordia spp. J Chem Soc Perkin I 1973; 1352-1357
• 31 Manners GD, Jurd L. The hydroquinone terpenoids of Cordia alliodora . J Chem Soc Perkin I 1977; 405-410
• 32 Niu XM, Li SH, Sun HD, Che CT. Prenylated phenolics from Ganoderma fornicatum . J Nat Prod 2006; 69: 1364-1365
• 33 Sevimli-Gur C, Akgun IH, Deliloglu-Gurhan I, Korkmaz KS, Bedir E. Cytotoxic naphthoquinones from Alkanna cappadocica . J Nat Prod 2010; 73: 860-864
• 34 Chen DF, Zhu HW, Li GX. Benzoquinone compound and its application in preparing antitumor drug.. CN Patent 103113335, 2013
• 35 Yoshizaki F, Hisamichi S, Kondo Y, Sato Y, Nozoe S. Studies on shikon. III. New furylhydroquinone derivatives, shikonofurans A, B, C, D and E, from Lithospermum erythrorhizon Sieb. Et Zucc. Chem Pharm Bull 1982; 30: 4407-4411
• 36 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55-63
• 37 Reed LJ, Muench H. A simple method of estimating fifty percent endpoints. Am J Hyg 1938; 27: 493-497