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Biotransformation of artemisinin derivatives by Glycyrrhiza glabra, Lavandula officinalis, and Panax quinquefolium

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Abstract

Biotransformation of α-artemether and dihydroartemisinin (DHA) by Glycyrrhiza glabra (Linn.), Lavandula officinalis (L.), and Panax quinquefolium was investigated. Two metabolites: tetrahydrofuran derivative (3) and a 13-carbon ring-rearranged product (4) were produced from α-artemether (1). DHA (2) provided metabolite 4. The structure of the metabolites were characterized by proton (1H) and carbon (13C) nuclear magnetic resonance (NMR) imaging, fourier transform infrared spectroscopy, and mass spectroscopy. This is the first report that G. glabra and L. officinalis have the capability to biotransform α-artemether, and P. quinquefolium to biotransform DHA. Metabolite 3 is a new compound and metabolite 4 is reported here for the first time from artemisinin derivatives 1 and 2. The presence of acetate function in the derivative 3 and hydroxyl and C-12 deoxo groups in 4 obtained in our study make them interesting synthones for further modification into new clinically potent molecules.

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References

  • Balint GA (2001) Artemisinin and its derivatives: an important new class of antimalarial agents. Pharmacol Ther 90:261–265

    Article  CAS  PubMed  Google Scholar 

  • Bhakuni RS, Jain DC, Sharma RP (2002) Phytochemistry of Artemisia annua and the development of artemisinin-derived antimalarial agents. In: Wright CW (ed) Artemisia. Medicinal and aromatic plants-industrial profiles, Taylor & Francis Inc., London, 18:211–247

  • Brisibe EA, Uyoh EA, Brisibe F, Magalha¨es PM, Ferreira JFS (2008) Building a golden triangle for the production and use of artemisinin derivatives against falciparum malaria in Africa. Afr J Biotechnol 7:4884–4896

    CAS  Google Scholar 

  • Chaturvedi D, Goswami A, Saikia PP, Barua NC, Rao PG (2010) Artemisinin and its derivatives: a novel class of anti-malarial and anti-cancer agents. Chem Soc Rev 39:435–454

    Article  CAS  PubMed  Google Scholar 

  • Dondorp A, Nosten F, Stepniewska K, Day N, White N (2006) Artesunate versus quinine for treatment of severe falciparum malaria: a randomized trial. Lancet 9487:717–725

    Google Scholar 

  • Giri A, Dhingra V, Giri CC, Singh A, Ward OP, Narasu ML (2001) Biotransformations using plant cells, organ cultures and enzyme systems: current trends and future prospects. Biotechnol Adv 19:175–199

    Article  CAS  PubMed  Google Scholar 

  • Jung M, Li X, Bustos DA, ElSohly HN, McChesney JD, Milhous WK (1990) Synthesis and antimalarial activity of (+)-deoxoartemisinin. J Med Chem 33:1516–1518

    Article  CAS  PubMed  Google Scholar 

  • Jung M, Lee K, Khim H, Park M (2004) Recent advances in artemisinin and its derivatives as antimalarial and antitumor agents. Curr Med Chem 11:1265–1284

    Article  CAS  PubMed  Google Scholar 

  • Kalita B, Barua NC, Bez G (2003) An unusual outcome in the wittig olefination of artemisinin and its derivatives under microwave irradiation. Ind J Chem B 42:2622–2624

    Google Scholar 

  • Khalifa SI, Baker JK, Jung M, McChesney JD, Hufford CD (1995) Microbial and mammalian metabolism studies on the semisynthetic antimalarial deoxoartemisinin. Pharm Res 12:1493–1498

    Article  CAS  PubMed  Google Scholar 

  • Klayman DL (1985) Qinghaosu (Artemisinin): an antimalarial drug from China. Science 228:1049–1055

    Article  CAS  PubMed  Google Scholar 

  • Lee IS, Hufford CD (1990) Metabolism of antimalarial sesquiterpene lactones. Pharmacol Ther 48:345–355

    Article  CAS  PubMed  Google Scholar 

  • Martensson A, Stromberg J, Sisowath C, Msellem MI, Gil JP, Montgomery SM, Olliaro P, Ali AS, Bjorkman A (2005) Efficacy of artesunate plus amodiaquine versus that of artemether–lumfantrine for the treatment of uncomplicated childhood Plasmodium falciparum malaria in Zanzibar, Tanzania. Clin Infect Dis 41:1079–1086

    Article  CAS  PubMed  Google Scholar 

  • Medeiros SF, Avery MA, Avery B, Leite SGF, Freitas Antonio CC, Williamson JS (2002) Biotransformation of 10-deoxoartemisinin to its 7β-hydroxy derivative by Mucor ramannianus. Biotech Lett 24:937–941

    Article  Google Scholar 

  • Musharraf SG, Uddin J, Akhter M, Saifullah PM, Khan S, Yousuf S, Khan S, Choudhary MI (2012) Biotransformation of an antimalarial drug artemether by plant and fungal cell cultures. J Mol Cat B 82:80–85

    Article  CAS  Google Scholar 

  • Park BK, O’Neill PM, Maggs JL, Pirmohamed M (1998) Safety assessment of peroxide antimalarials: clinical and chemical perspectives. Br J Clin Pharmacol 46:521–529

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Patel S, Gaur R, Verma P, Bhakuni RS, Mathur A (2010) Biotransformation of artemisinin using cell suspension cultures of Catharanthus roseus (L.) Lavandula officinalis. Biotech Lett 32:1167–1171

    Article  CAS  Google Scholar 

  • Patel S, Gaur R, Upadhyaya M, Mathur A, Mathur AK, Bhakuni RS (2011) Glycyrrhiza glabra (Linn.) and Lavandula officinalis (L.) cell suspension cultures-based biotransformation of β-artemether. J Nat Med 65:646–650

    Article  CAS  PubMed  Google Scholar 

  • Shams AM, Ghannadi A, Badr P, Mohagheghzadeh A (2005) Biotransformation of terpenes and related compounds by suspension culture of Glycyrrhiza glabra L. (Papilionaceae). Flavour Fragr J 20:141

    Article  Google Scholar 

  • Shams AM, Linley PA, Harkiss KJ, Mohagheghzadeh A, Gholami A, Mosaddegh M (2007) Biotransformation of monoterpenoids by suspension culture s of Lavandula angustifolia. Iran J Pharm Sci 3:93–100

    Google Scholar 

  • Wei GF, Liao XJ, Pan GY, Huang ZL, JS Cheng, He YC (2010) Facile one-pot conversion and characterization of dihydroartemisinin and artemether. J Natl Prod 161–164

  • Wu WM, Wu YK, Wu YL, Yao ZJ, Zhou CM, Li Y, Shan F (1998) Unified mechanistic pathway for the Fe(II)—Induced cleavage of Quinghaosu and derivatives/Analougs: the first spin- trapping evidence for the previously postulated secondary C-4 radical. J Am Chem Soc 120:3316–3325

    Article  CAS  Google Scholar 

  • Yang ZH, Zeng R, Yang G, Wang Y, Li LZ, Lv ZS, Yao M, Lai B (2008) Asymmetric reduction of prochiral ketones to chiral alcohols catalyzed by plants tissue. J Ind Microbiol Biotechnol 35:1047–1051

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We wish to thank Director CIMAP, Lucknow, for providing the necessary facilities and constant encouragement to carry out this study. The work was carried out under a major laboratory project (MLP-02) on “Exploration of bioactive molecules from Natural sources and value addition through semi-synthetic approach.”

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Authors and Affiliations

  1. Medicinal Plant Chemistry Division, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow, 226015, India

    Rashmi Gaur & Rajendra Singh Bhakuni

  2. Plant Biotechnology Division, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow, 226015, India

    Suman Patel & Archana Mathur

  3. Analytical Chemistry Division, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow, 226015, India

    Ram Kishor Verma

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  1. Rashmi Gaur
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  2. Suman Patel
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  3. Ram Kishor Verma
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  4. Archana Mathur
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  5. Rajendra Singh Bhakuni
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Correspondence to Rajendra Singh Bhakuni.

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Gaur, R., Patel, S., Verma, R.K. et al. Biotransformation of artemisinin derivatives by Glycyrrhiza glabra, Lavandula officinalis, and Panax quinquefolium . Med Chem Res 23, 1202–1206 (2014). https://doi.org/10.1007/s00044-013-0726-x

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  • DOI: https://doi.org/10.1007/s00044-013-0726-x

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