Antiprotozoal Diterpenes from Perovskia abrotanoides

Marzieh Tabefam; Mahdi Moridi Farimani; Ombeline Danton; Justine Ramseyer; Marcel Kaiser; Samad N. Ebrahimi; Peyman Salehi; Hossien Batooli; Olivier Potterat; Matthias Hamburger

doi:10.1055/a-0608-4946

Planta Medica, Table of Contents

Planta Med 2018; 84(12/13): 913-919
DOI: 10.1055/a-0608-4946

Natural Product Chemistry and Analytical Studies

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Antiprotozoal Diterpenes from Perovskia abrotanoides ^[*]

Marzieh Tabefam

¹Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran

²Division of Pharmaceutical Biology, University of Basel, Switzerland

,

Mahdi Moridi Farimani

¹Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran

,

Ombeline Danton

²Division of Pharmaceutical Biology, University of Basel, Switzerland

,

Justine Ramseyer

²Division of Pharmaceutical Biology, University of Basel, Switzerland

,

Marcel Kaiser

³Swiss Tropical and Public Health Institute, Basel, Switzerland

⁴University of Basel, Basel, Switzerland

,

Samad N. Ebrahimi

¹Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran

,

Peyman Salehi

¹Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran

,

Hossien Batooli

⁵Kashan Botanical Garden, Research Institute of Forests and Rangelands, Agricultural Research, Education and Extension Organization (AREEO), Tehran, Iran

,

Olivier Potterat

²Division of Pharmaceutical Biology, University of Basel, Switzerland

,

Matthias Hamburger

²Division of Pharmaceutical Biology, University of Basel, Switzerland

› Author Affiliations

Abstract

As part of a screening for new antiparasitic natural products from Iranian plants, n-hexane and ethyl acetate extracts from the aerial parts of Perovskia abrotanoides were found to exhibit strong inhibitory activity against Trypanosoma brucei rhodesiense and Leishmania donovani. The activity was tracked by high-performance liquid chromatography (HPLC)-based activity profiling. Preparative isolation by a combination of silica gel column chromatography and HPLC afforded 17 diterpenoids (1–17), including 14 abietane-, two icetexane-, and one isopimarane-type derivatives. Among these, (5R,10S)-11-hydroxy-12-methoxy-20-norabieta-8,11,13-triene (2), 12-hydroxy-norabieta-1(10),8,11,13-tetraene-1,11-furan (6), and 12-methoxybarbatusol (9) were new compounds, the structure of which was established by comprehensive spectroscopic data analysis (one- and two-dimensional nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, electronic circular dichroism). The antiprotozoal activity of the isolated compounds was evaluated against T. b. rhodesiense, Trypanosoma cruzi, L. donovani, and Plasmodium falciparum. Selectivity indexes (SI) were calculated in comparison to cytotoxicity on rat myoblast (L6) cells. Particularly active were 7α-ethoxyrosmanol (4) with an IC₅₀ of 0.8 µM against T. b. rhodesiense (SI 14.9) and an IC₅₀ of 1.8 µM (SI 6.9) against L. donovani, ferruginol (8) with an IC₅₀ of 2.9 µM (SI 19.2) against P. falciparum, and miltiodiol (10) with an IC₅₀ of 0.5 µM (SI 10.5) against T. b. rhodesiense. None of the compounds exhibited selective toxicity against T. cruzi (SI ≤ 1.6).

Key words

Perovskia abrotanoides - Lamiaceae - diterpenoids - Leishmania donovani - Trypanosoma brucei rhodesiense - Plasmodium falciparum

Full Text

References

References
1 Rechinger KH. In: Rechinger KH, Hedge IC. eds. Flora Iranian Labiatae. Graz, Austria: Akademische Druck and Verlagsanstalt; 1982: 350 370, 477
2 Sairafianpour M, Christensen J, Stærk D, Budnik BA, Kharazmi A, Bagherzadeh K, Jaroszewski JW. Leishmanicidal, antiplasmodial, and cytotoxic activity of novel diterpenoid 1, 2-quinones from Perovskia abrotanoides: new source of tanshinones. J Nat Prod 2001; 64: 1398-1403
3 Jiang ZY, Zhu LY, Zhou J, Hu QF, Yang GY, Huang XZ, Liu WX, Gao L, Li GP, Xia FT. A novel C22 terpenoid from the cultured Perovskia atriplicifolia . Helv Chim Acta 2016; 99: 452-456
4 Jiang ZY, Huang CG, Xiong HB, Tian K, Liu WX, Hu QF, Wang HB, Yang GY, Huang XZ. Perovskatone A: a novel C23 terpenoid from Perovskia atriplicifolia . Tetrahedron Lett 2013; 54: 3886-3888
5 Jiang ZY, Zhou J, Huang CG, Hu QF, Huang XZ, Wang W, Zhang LZ, Li GP, Xia FT. Two novel antiviral terpenoids from the cultured Perovskia atriplicifolia . Tetrahedron 2015; 71: 3844-3849
6 Ahmad VU, Parvez A, Hassan N. Isolation and structure determination of peradione (1) a novel triterpene with a rearranged perovskane skeleton from Perovskia abrotanoides . Tetrahedron Lett 1993; 34: 5337-5340
7 Parvez A, Choudhary MI, Akhter F, Noorwala M, Mohammad FV, Hasan NM, Zamir T, Ahmad VU. Perovskone: a triterpene with a novel carbon skeleton from Perovskia abrotanoides . J Org Chem 1992; 57: 4339-4340
8 Cao EH, Liu XQ, Wang JJ, Xu NF. Effect of natural antioxidant tanshinone II-A on DNA damage by lipid peroxidation in liver cells. Free Radic Biol Med 1996; 20: 801-806
9 Lee DS, Lee SH, Noh JG, Hong SD. Antibacterial activities of cryptotanshinone and dihydrotanshinone I from a medicinal herb, Salvia miltiorrhiza Bunge. Biosci Biotechnol Biochem 1999; 63: 2236-2239
10 Kim EJ, Jung SN, Son KH, Kim SR, Ha TY, Park MG, Jo IG, Park JG, Choe W, Kim SS. Antidiabetes and antiobesity effect of cryptotanshinone via activation of AMP-activated protein kinase. Mol Pharmacol 2007; 72: 62-72
11 Jang SI, Jeong SI, Kim KJ, Kim HJ, Yu HH, Park R, Kim HM, You YO. Tanshinone IIA from Salvia miltiorrhiza inhibits inducible nitric oxide synthase expression and production of TNF-α, IL-1β and IL-6 in activated RAW 264.7 cells. Planta Med 2003; 69: 1057-1059
12 Wang X, Wei Y, Yuan S, Liu G, Lu Y, Zhang J, Wang W. Potential anticancer activity of tanshinone IIA against human breast cancer. Int J Cancer 2005; 116: 799-807
13 Moridi Farimani M, Bahadori MB, Taheri S, Ebrahimi SN, Zimmermann S, Brun R, Amin G, Hamburger M. Triterpenoids with rare carbon skeletons from Salvia hydrangea: antiprotozoal activity and absolute configurations. J Nat Prod 2011; 74: 2200-2205
14 Ebrahimi SN, Zimmermann S, Zaugg J, Smiesko M, Brun R, Hamburger M. Abietane diterpenoids from Salvia sahendica – antiprotozoal activity and determination of their absolute configurations. Planta Med 2013; 29: 150-156
15 Hata Y, Zimmermann S, Quitschau M, Kaiser M, Hamburger M, Adams M. Antiplasmodial and antitrypanosomal activity of pyrethrins and pyrethroids. J Agric Food Chem 2011; 59: 9172-9176
16 Ślusarczyk S, Zimmermann S, Kaiser M, Matkowski A, Hamburger M, Adams M. Antiplasmodial and antitrypanosomal activity of tanshinone-type diterpenoids from Salvia miltiorrhiza . Planta Med 2011; 77: 1594-1596
17 Farimani MM, Taheri S, Ebrahimi SN, Bahadori MB, Khavasi HR, Zimmermann S, Brun R, Hamburger M. Hydrangenone, a new isoprenoid with an unprecedented skeleton from Salvia hydrangea . Org Lett 2011; 14: 166-169
18 Zimmermann S, Kaiser M, Brun R, Hamburger M, Adams M. Cynaropicrin: the first plant natural product with in vivo activity against Trypanosoma brucei . Planta Med 2012; 78: 553-556
19 Adams M, Zimmermann S, Kaiser M, Brun R, Hamburger M. A protocol for HPLC-based activity profiling for natural products with activities against tropical parasites. Nat Prod Commun 2009; 4: 1377-1381
20 Potterat O, Hamburger M. Combined use of extract libraries and HPLC-based activity profiling for lead discovery: potential, challenges, and practical considerations. Planta Med 2014; 80: 1171-1181
21 Kido H, Ii S. Antibacterial agent and disinfecting method. US patent 20130150456A1; 2013.
22 Fischedick JT, Standiford M, Johnson DA, Johnson JA. Structure activity relationship of phenolic diterpenes from Salvia officinalis as activators of the nuclear factor E2-related factor 2 pathway. Bioorg Med Chem 2013; 21: 2618-2622
23 Marrero JG, Andrés LS, Luis JG. Semisynthesis of rosmanol and its derivatives. Easy access to abietatriene diterpenes isolated from the genus Salvia with biological activities. J Nat Prod 2002; 65: 986-989
24 Jassbi AR, Eghtesadi F, Hazeri N, Maʼsumi H, Valizadeh J, Chandran JN, Schneider B, Baldwin IT. The roots of Salvia rhytidea: a rich source of biologically active diterpenoids. Nat Prod Res 2017; 31: 477-481
25 Haslinger E, Michl G. Synthese von (+)-Taxodion. Eur J Org Chem 1989; 1989: 677-686
26 Naman CB, Gromovsky AD, Vela CM, Fletcher JN, Gupta G, Varikuti S, Zhu X, Zywot EM, Chai H, Werbovetz KA. Antileishmanial and cytotoxic activity of some highly oxidized abietane diterpenoids from the bald cypress, Taxodium distichum . J Nat Prod 2016; 79: 598-606
27 Fronza M, Murillo R, Ślusarczyk S, Adams M, Hamburger M, Heinzmann B, Laufer S, Merfort I. In vitro cytotoxic activity of abietane diterpenes from Peltodon longipes as well as Salvia miltiorrhiza and Salvia sahendica . Bioorg Med Chem 2011; 19: 4876-4881
28 Majetich G, Zou G. Total synthesis of (−)-barbatusol, (+)-demethylsalvicanol, (−)-brussonol, and (+)-grandione. Org Lett 2008; 10: 81-83
29 Majetich G, Liu S, Fang J, Siesel D, Zhang Y. Use of conjugated dienones in cyclialkylations: total syntheses of arucadiol, 1,2-didehydromiltirone, (±)-hinokione, (±)-nimbidiol, sageone, and miltirone. J Org Chem 1997; 62: 6928-6951
30 Garbarino JA, Molinari A. Diterpenes from Calceolaria latifolia . Phytochemistry 1990; 29: 3037-3039
31 Aoyagi Y, Takahashi Y, Satake Y, Takeya K, Aiyama R, Matsuzaki T, Hashimoto S, Kurihara T. Cytotoxicity of abietane diterpenoids from Perovskia abrotanoides and of their semisynthetic analogues. Bioorg Med Chem 2006; 14: 5285-5291
32 Argay G, Kálmán A, Ribár B, Djarmati Z, Tot N, Schwirtlich E, Jankov RM. Crystal structure of rosmanol-9-ethylether. J Chem Crystallogr 1991; 21: 625-628
33 Fraga BM, Díaz CE, Guadaño A, González-Coloma A. Diterpenes from Salvia broussonetii transformed roots and their insecticidal activity. J Agric Food Chem 2005; 53: 5200-5206
34 Alegre-Gómez S, Sainz P, Simões MF, Rijo P, Moiteiro C, González-Coloma A, Martínez-Díaz RA. Antiparasitic activity of diterpenoids against Trypanosoma cruzi . Planta Med 2017; 83: 306-311
35 Machumi F, Samoylenko V, Yenesew A, Derese S, Midiwo JO, Wiggers FT, Jacob MR, Tekwani BL, Khan SI, Walker LA. Antimicrobial and antiparasitic abietane diterpenoids from the roots of Clerodendrum eriophyllum . Nat Prod Commun 2010; 5: 853
36 Jassbi AR, Zare S, Firuzi O, Xiao J. Bioactive phytochemicals from shoots and roots of Salvia species. Phytochem Rev 2016; 15: 829-867
37 Naman CB, Gromovsky AD, Vela CM, Fletcher JN, Gupta G, Varikuti S, Zhu X, Zywot EM, Chai H, Werbovetz KA. Antileishmanial and cytotoxic activity of some highly oxidized abietane diterpenoids from the bald cypress, Taxodium distichum . J Nat Prod 2016; 79: 598-606
38 Mothana RA, Al-Said MS, Al-Musayeib NM, Gamal AAE, Al-Massarani SM, Al-Rehaily AJ, Abdulkader M, Maes L. In vitro antiprotozoal activity of abietane diterpenoids isolated from Plectranthus barbatus Andr. Int J Mol Sci 2014; 15: 8360-8371
39 Orhan I, Şener B, Kaiser M, Brun R, Tasdemir D. Inhibitory activity of marine sponge-derived natural products against parasitic protozoa. Mar Drugs 2010; 8: 47-58
40 Huber W, Koella JC. A comparison of three methods of estimating EC₅₀ in studies of drug resistance of malaria parasites. Acta Trop 1993; 55: 257-261
41 Frisch M, Trucks G, Schlegel H, Scuseria G, Robb M, Cheeseman J, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ. Gaussian 09, Revision A02. Wallingford CT: Gaussian, Inc.; 2009
42 Bruhn T, Schaumlöffel A, Hemberger Y, Bringmann G. SpecDis: quantifying the comparison of calculated and experimental electronic circular dichroism spectra. Chirality 2013; 25: 243-249

Supplementary Material

Supporting Information

Antiprotozoal Diterpenes from Perovskia abrotanoides [*]

Antiprotozoal Diterpenes from Perovskia abrotanoides ^[*]