Skip to main content
SpringerLink
Log in

Synthesis and reactive oxygen species scavenging activity of halogenated alkaloids from boldine

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

Six halogenated alkaloids have been semi-synthesized from natural boldine as starting material. Their antioxidant activity toward reactive oxygen species (ROS) generation by neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine and in the hypoxanthine–xanthine oxidase system was evaluated. Most of the alkaloids synthesized inhibited ROS generation in both systems in a concentration-dependent manner. The alkaloids with phenolic substituents displayed more powerful anti-oxidative activity than those containing methoxylated groups. None of the alkaloids assayed had any effect on xanthine oxidase activity. Therefore, halogenated phenanthrene alkaloids can become in promising candidates for the development of novel and potent anti-inflammatory drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Bauerova K, Bezek A (1999) Role of reactive oxygen and nitrogen species in etiopathogenesis of rheumatoid arthritis. Gen Physiol Biophys 18 Spec No 15–20

    Google Scholar 

  • Beckman JS, Parks DA, Pearson JD, Marshall PA, Freeman BA (1989) A sensitive fluorometric assay for measuring xanthine dehydrogenase and oxidase in tissues. Free Radic Biol Med 6:607–615

    Article  PubMed  CAS  Google Scholar 

  • Cederbaum AI, Kukielka E, Speisky H (1992) Inhibition of rat liver microsomal lipid peroxidation by boldine. Biochem Pharmacol 44:1765–1772

    Article  PubMed  CAS  Google Scholar 

  • Dinkova-Kostova AT (2008) Phytochemicals as protectors against ultraviolet radiation: versatility of effects and mechanisms. Planta Med 74:1548–1559

    Article  PubMed  CAS  Google Scholar 

  • Estellés R, López-Martín J, Milián L, O’Connor JE, Martínez-Losa M, Cerdá-Nicolás M, Anam EM, Ivorra MD, Issekutz AC, Cortijo J, Morcillo EJ, Blázquez MA, Sanz MJ (2003) Effect of two phenanthrene alkaloids on angiotensin II-induced leukocyte-endothelial cell interactions in vivo. Br J Pharmacol 140:1057–1067

    Article  PubMed  Google Scholar 

  • Estellés R, Milián L, Nabah YN, Mateo T, Cerdá-Nicolás M, Losada M, Ivorra MD, Issekutz AC, Cortijo J, Morcillo EJ, Blázquez MA, Sanz MJ (2005) Effect of boldine, secoboldine, and boldine methine on angiotensin II-induced neutrophil recruitment in vivo. J Leukoc Biol 78:696–704

    Article  PubMed  Google Scholar 

  • Gaboury JP, Anderson DC, Kubes P (1994) Molecular mechanisms involved in superoxide-induced leukocyte-endothelial cell interactions in vivo. Am J Physiol 266:H637–H642

    PubMed  CAS  Google Scholar 

  • García MT, Blázquez MA, Ferrándiz MJ, Sanz MJ, Silva-Martín N, Hermoso JA, De la Campa AG (2011) New alkaloid antibiotics that target the DNA topoisomerase I of Streptococcus pneumoniae. J Biol Chem 286:6402–6413

    Article  PubMed  Google Scholar 

  • Gerhardt D, Horn AP, Gaelzer MM, Frozza RL, Delgado-Cañedo A, Pelegrini AL, Henriques AT, Lenz G, Salbego C (2009) Boldine: a potential new antiproliferative drug against glioma cell lines. Investig New Drugs 27:517–525

    Article  CAS  Google Scholar 

  • Griendling KK, Sorescu D, Ushio-Fukai M (2000) NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 86:494–501

    Article  PubMed  CAS  Google Scholar 

  • Guzman JD, Gupta A, Evangelopoulos D, Basavannacharya C, Pabon LC, Plazas EA, Muñoz DR, Delgado WA, Cuca LE, Ribon W, Gibbons S, Bhakta S (2010) Anti-tubercular screening of natural products from Colombian plants: 3-methoxynordomesticine, an inhibitor of MurE ligase of Mycobacterium tuberculosis. J Antimicrob Chemother 65:2101–2107

    Article  PubMed  CAS  Google Scholar 

  • Iturriaga-Vásquez P, Pérez EG, Slater EY, Bermúdez I, Cassels BK (2007) Aporphine metho salts as neuronal nicotinic acetylcholine receptor blockers. Bioorg Med Chem 15:3368–3372

    Article  PubMed  Google Scholar 

  • Jaeschke H (1995) Mechanisms of oxidant stress-induced acute tissue injury. Proc Soc Exp Biol Med 209:104–111

    PubMed  CAS  Google Scholar 

  • Jang YY, Song JH, Shin YK, Han ES, Lee CS (2000) Protective effect of boldine on oxidative mitochondrial damage in streptozotocin-induced diabetic rats. Pharmacol Res 42:361–371

    Article  PubMed  CAS  Google Scholar 

  • Johnston B, Kanwar S, Kubes P (1996) Hydrogen peroxide induces leukocyte rolling: modulation by endogenous antioxidant mechanisms including NO. Am J Physiol 271:H614–H621

    PubMed  CAS  Google Scholar 

  • López-Martín J, Anam EM, Boira H, Sanz MJ, Blázquez MA (2002) Chromone and phenanthrene alkaloids from Dennettia tripetala. Chem Pharm Bull (Tokyo) 50:1613–1615

    Article  Google Scholar 

  • Martínez LA, Ríos JL, Payá M, Alcaraz MJ (1992) Inhibition of nonenzymic lipid peroxidation by benzylisoquinoline alkaloids. Free Radic Biol Med 12:287–292

    Article  PubMed  Google Scholar 

  • Martínez S, Madrero Y, Elorriaga M, Noguera MA, Cassels B, Sobarzo E, D’Ocón P, Ivorra MD (1999) Halogenated derivatives of boldine with high selectivity for alpha1A-adrenoceptors in rat cerebral cortex. Life Sci 64:1205–1214

    Article  PubMed  Google Scholar 

  • Milián L, Estellés R, Abarca B, Ballesteros R, Sanz MJ, Blázquez MA (2004) Reactive oxygen species (ROS) generation inhibited by aporphine and phenanthrene alkaloids semi-synthesized from natural boldine. Chem Pharm Bull (Tokyo) 52:696–699

    Article  Google Scholar 

  • Rancan F, Rosan S, Boehm K, Fernandez E, Hidalgo ME, Quihot W, Rubio C, Boehm F, Piazena H, Oltmanns U (2002) Protection against UVB irradiation by natural filters extracted from lichens. J Photochem Photobiol B 68:133–139

    Article  PubMed  CAS  Google Scholar 

  • Riaz AA, Schramm R, Sato T, Menger MD, Jeppsson B, Thorlacius H (2003) Oxygen radical-dependent expression of CXC chemokines regulate ischemia/reperfusion-induced leukocyte adhesion in the mouse colon. Free Radic Biol Med 35:782–789

    Article  PubMed  CAS  Google Scholar 

  • Schudt C, Winder S, Forderkunz S, Hatzelmann A, Ullrich V (1991) Influence of selective phosphodiesterase inhibitors on human neutrophil functions and levels of cAMP and Cai. Naunyn Schmiedebergs Arch Pharmacol 344:682–690

    Article  PubMed  CAS  Google Scholar 

  • Sekiguchi T, Nagamine T (1994) Inhibition of free radical generation by biotin. Biochem Pharmacol 47:594–596

    Article  PubMed  CAS  Google Scholar 

  • Sobarzo-Sánchez E, Julian C, Cassels BK, Saitz C (2002) New heterocyclic skeletons derived from aporphine alkaloid boldine. Synth Commun 32:3687–3693

    Article  Google Scholar 

  • Speisky H, Cassels BK, Lissi EA, Videla LA (1991) Antioxidant properties of the alkaloid boldine in systems undergoing lipid peroxidation and enzyme inactivation. Biochem Pharmacol 41:1575–1581

    Article  PubMed  CAS  Google Scholar 

  • Youn YC, Kwon OS, Han ES, Song JH, Shin YK, Lee CS (2002) Protective effect of boldine on dopamine-induced membrane permeability transition in brain mitochondria and viability loss in PC12 cells. Biochem Pharmacol 63:495–505

    Article  PubMed  CAS  Google Scholar 

  • Yu B, Cook C, Santanam N (2009) The aporphine alkaloid boldine induces adiponectin expression and regulation in 3T3-L1 cells. J Med Food 12:1074–1083

    Article  PubMed  CAS  Google Scholar 

  • Zhao B (2009) Natural antioxidants protect neurons in Alzheimer’s disease and Parkinson’s disease. Neurochem Res 34:630–638

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This study was supported by grants SAF2008-03477 and Project CONSOLIDER-INGENIO SUPRAMED CSD 2010-00065 and Generalitat Valenciana PROMETEO/2011/008, Spanish Ministry of Science and Innovation and RIER RD08/0075/0016, Carlos III Health Institute, Spanish Ministry of Health. L. Milián was supported by a grant from the Spanish Ministry of Science and Innovation.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100, Burjassot, Valencia, Spain

    Lara Milián & María Amparo Blázquez

  2. Department of Organic Chemistry, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100, Burjassot, Valencia, Spain

    Rafael Ballesteros

  3. Department of Pharmacology, Faculty of Medicine, University of Valencia, Av. Blasco Ibáñez 15, 46013, Valencia, Spain

    María Jesús Sanz

Authors
  1. Lara Milián
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rafael Ballesteros
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. María Jesús Sanz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. María Amparo Blázquez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to María Amparo Blázquez.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Milián, L., Ballesteros, R., Sanz, M.J. et al. Synthesis and reactive oxygen species scavenging activity of halogenated alkaloids from boldine. Med Chem Res 21, 3133–3139 (2012). https://doi.org/10.1007/s00044-011-9844-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-011-9844-5

Keywords

Search

Navigation