Planta Med 2011; 77(1): 77-80
DOI: 10.1055/s-0030-1250144
Natural Product Chemistry
Letters
© Georg Thieme Verlag KG Stuttgart · New York

Leishmanicidal and Reversal Multidrug Resistance Constituents from Aeonium lindleyi

María L. Kennedy1 , 2 , Fernando Cortés3 , José E. Piñero4 , Santiago Castanys3 , Atteneri López-Arencibia4 , Francisco Gamarro3 , Isabel L. Bazzocchi1 , Ignacio A. Jiménez1
  • 1Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, La Laguna, Tenerife, Spain
  • 2Facultad de Ciencias Químicas, Universidad Nacional de Asunción, Campus UNA, San Lorenzo, Paraguay
  • 3Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Parque Tecnológico de Ciencias de la Salud, Granada, Spain
  • 4Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Departamento de Parasitología, Ecología y Genética, Facultad de Farmacia, Universidad de La Laguna, La Laguna, Tenerife, Spain
Weitere Informationen

Publikationsverlauf

received February 9, 2010 revised June 22, 2010

accepted June 24, 2010

Publikationsdatum:
21. Juli 2010 (online)

Abstract

A new bicyclic diterpene with a labdane skeleton, 7-oxo-labd-8-en-15-ol (1), along with two known diterpenes and ten flavonoids were isolated from the leaves of Aeonium lindleyi (Crassulaceae). Their structures were elucidated on the basis of spectroscopic data, including 1D and 2D NMR experiments, and comparison with spectroscopic data reported in the literature. Labdan-8α,15-diol (2) and labd-8(17)-en-3β,15-diol (3) showed leishmanicidal activity against Leishmania tropica (IC50 = 77.0 µM) and Leishmania braziliensis (IC50 = 68.0 µM) similar to ketoconazole used as positive control. 5,3′-Dihydroxy-3,7,4′,5′-tetramethoxyflavone (8) and combretol (9) showed moderate activity (growth inhibition 87.3 and 73.0 %, respectively, at 50 µM) against a multidrug-resistant L. tropica line.

References

  • 1 Cruz A K, Simoes de Toledo J, Falade M, Terrao M C, Kamchonwongpaisan S, Kyle D E, Uthaipibull C. Current treatment and drug discovery against Leishmania spp. and Plasmodium spp.: a review.  Curr Drug Targets. 2009;  10 178-192
  • 2 Sauvage V, Aubert D, Escotte-Binet S, Villena I. The role of ATP-binding cassette (ABC) proteins in protozoan parasites.  Mol Biochem Parasitol. 2009;  167 81-94
  • 3 Pérez-Victoria J M, Pérez-Victoria F J, Parodi-Talice A, Jiménez I A, Ravelo A G, Castanys S, Gamarro F. Alkyl-lysophospholipid resistance in multidrug-resistant Leishmania tropica and chemosensitization by a novel P-glycoprotein-like transporter modulator.  Antimicrob Agents Chemother. 2001;  45 2468-2474
  • 4 Berman J J. Treatment of leishmaniasis with miltefosine: 2008 status.  Expert Opin Drug Metab Toxicol. 2008;  4 1209-1216
  • 5 Pérez-Victoria J M, Di Pietro A, Barron D, Ravelo A G, Castanys S, Gamarro F. Multidrug resistance phenotype mediated by the P-glycoprotein-like transportes in Leishmania: a search for reversal agents.  Curr Drug Targets. 2002;  3 311-333
  • 6 Bansal T, Jaggi M, Khar R K, Talegaonkar S. Emerging significance of flavonoids as P-glycoprotein inhibitors in cancer chemotherapy.  J Pharm Pharm Sci. 2009;  12 46-78
  • 7 Kabouche A, Kabouche Z. Bioactive diterpenoids of Salvia species. In: Atta-ur-Rahman FRS, editor. Studies in natural products chemistry. Bioactive natural products.  Amsterdam: Elsevier. 2008;  35 753-834
  • 8 Pérez de Paz P L, Hernández C P. Plantas Medicinales o Útiles en la Flora Canaria. Tenerife, España; F. Lemus 1999: 99-100
  • 9 Darias V, González A G, Boada J N, Feria M, Martorell F. Pharmacological study of lindleyin.  Farmaco Sci. 1978;  33 460-467
  • 10 Stevens J, Hart H, Wollenweber E. The systematic and evolutionary significance of exudates flavonoids in Aeonium.  Phytochemistry. 1995;  39 805-813
  • 11 Baker A J, Eglinton G, González A G, Hamilton R J, Raphael R A. A new leaf-gum constituent: labdane-8α,15-diol.  J Chem Soc. 1962;  16 4705-4709
  • 12 Chandra G, Clark J, McLean J, Pauson P L, Watson J, Reed R I, Tabrizi F M. A new diterpene from Araucaria imbricata.  J Chem Soc. 1964;  3648-3654
  • 13 Harborne J B, Mabry T J, Mabry H. The flavonoids. Part 1. London; Academic Press 1975 324-331 564
  • 14 Harborne J B. Correlations between flavonoid chemistry, anatomy and geography in the Restionaceae.  Phytochemistry. 1979;  18 1323-1327
  • 15 Harborne J B, Boardley M, Lindlert H P. Variations in flavonoid patterns within the genus Chondropetalum (Restionaceae).  Phytochemistry. 1985;  24 273-278
  • 16 Weyerstahl P, Marschall H, Weirauch M, Thefeld K, Surburg H. Constituents of commercial labdanum oil.  Flavour Fragr J. 1998;  13 295-318
  • 17 Fokialakis N, Kalpoutzakis E, Tekwani B, Skaltsounis A L, Duke S O. Antileishmanial activity of natural diterpenes from Cistus sp. and semisynthetic derivatives thereof.  Biol Pharm Bull. 2006;  29 1775-1778
  • 18 Vermeersch M, da Luz R I, Toté K, Timmermans J P, Cos P, Maes L. In vitro susceptibilities of Leishmania donovani promastigote and amastigote stages to antileishmanial reference drugs: practical relevance of stage-specific differences.  Antimicrob Agents Chemother. 2009;  53 3855-3859
  • 19 Conseil G, Baubichon-Cortay H, Dayan G, Jault J-M, Barron D, Di Peitro A. Flavonoids: a class of modulators with bifunctional interactions at vicinal ATP- and steroid-binding sites on mouse P-glycoprotein.  Proc Natl Acad Sci USA. 1998;  95 9831-9836
  • 20 Cabrera-Serra M G, Lorenzo-Morales J, Romero M, Valladares B, Piñero J E. In vitro activity of perifosine: a novel alkylphospholipid against the promastigote stage of Leishmania species.  Parasitol Res. 2007;  100 1155-1157
  • 21 Cortés-Selva F, Campillo M, Reyes C P, Jiménez I A, Castanys S, Bazzocchi I L, Pardo L, Gamarro F, Ravelo A G. SAR studies of dihidro-β-agarofuran sesquiterpenes as inhibitors of multidrug-resistance phenotype in a Leishmania tropica line overexpressing a P-glycoprotein-like transporter.  J Med Chem. 2004;  47 576-587

Ignacio A. Jiménez

Instituto Universitario de Bio-Orgánica “Antonio González”
Universidad de La Laguna

Avenida Astrofísico Francisco Sánchez, 2

38206 La Laguna

Tenerife

Spain

Telefon: + 34 9 22 31 85 94

Fax: + 34 9 22 31 85 71

eMail: ignadiaz@ull.es