Planta Med 2003; 69(11): 1060-1062
DOI: 10.1055/s-2003-45158
Letter
© Georg Thieme Verlag Stuttgart · New York

2-(4′-Aminobenzenamine)-pyrimidine, A New α-Antagonist from Autonoë madeirensis

Catarina Dias1 , Alexandra Paulo1 , José Nascimento1 , Peter Houghton2 , Jane E. Hawkes3 , M. Lurdes Gonçalves4
  • 1CECF, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal
  • 2Pharmacognosy Research Laboratories, Department of Pharmacy, King’s College London, London, U.K.
  • 3Department of Chemistry, King's College, University of London, Strand, London, UK.
  • 4Unit of Pharmacology and Pharmacotoxicology, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal
This research was carried out with financial support from Fundação para a Ciência e Tecnologia (POCTI/FEDER)
Further Information

Publication History

Received: June 2, 2003

Accepted: August 10, 2003

Publication Date:
09 January 2004 (online)

Abstract

A new natural pyrimidine derivative, 2-(4′-aminobenzenamine)-pyrimidine (1), was isolated from the bulbs of Autonoë madeirensis, a Hyacinthaceae of the Madeira Archipelago (Portugal) and the structure determined on the basis of spectroscopic data. As some pyrimidine compounds are important α1-adrenergic antagonists, we investigated the effect of 1 on rat vas deferens contractility induced by the α1-agonist phenylephrine. In concentrations virtually devoid of effect on the rat vas deferens contractility, 1 shifted to the right the concentration-response curves of phenylephrine without changing the maximal effect. These results provide evidence that 1 acts as an α1-adrenoceptor antagonist and suggest a competitive mechanism of action.

References

  • 1 Menezes C A. Novos subsídios para o estudo da flora do Arquipélago da Madeira.  Brotéria Série Botânica. 1926;  22 24-5
  • 2 Brummitt R K. Vascular Plant Families and Genera. Kew; Royal Botanic Gardens 1992: p. 389 and 721
  • 3 Speta F. Systematische Analyse der Gattung Scilla L. s. l. (Hyacinthaceae).  Phyton. 1998;  38 87-95 and 121 - 3
  • 4 Dias C, Graça J A, Gonçalves M L. Scilla maderensis, TLC screening and positive inotropic effect of bulb extracts.  J Ethnopharmacol. 2000;  71 487-92
  • 5 Foye W O, Lemke T L, Williams D A, editors. Principles of Medicinal Chemistry. Philadelphia; Lippincott Williams & Wilkins 1995: pp. 358-9
  • 6 Narayan P, Tewari A. Overview of α-blocker therapy for benign prostatic hyperplasia.  Urology. 1998;  51 38-45
  • 7 Meyer M D, Altenbach R J, Basha F Z, Carroll W A, Drizin I, Elmore S W. et al . Synthesis and pharmacological characterization of 3-[2-((3aR,9bR)-cis-6-methoxy-2,3,3a,4,5,9b-hexahydro-1H-benz[e]isoindol-2-yl)ethyl] pyrido-[3′,4′:4,5]thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione (A-131 701): A uroselective α1A adrenoceptor antagonist for the symptomatic treatment of benign prostatic hyperplasia.  J Med Chem. 1997;  40 3141-3
  • 8 Barrow J C, Nantermet P G, Selnick H G, Glass K L, Rittle K E, Gilbert K F. et al . In vitro and in vivo evaluation of dihydropyrimidinone C-5 amides as potent and selective α-1A receptor antagonists for the treatment of benign prostatic hyperplasia.  J Med Chem. 2000;  43 2703-18
  • 9 Hancock A A, Buckner S A, Brune M E, Esbenshade T A, Ireland L M, Katwala S. et al . Preclinical pharmacology of fiduxosin, a novel α1-adrenoceptor antagonist with uroselective properties.  J Pharmacol Exp Ther. 2002;  300 478-86
  • 10 Koch E. Extracts from fruits of Saw Palmetto (Sabal serrulata) and roots of stinging nettle (Urtica dioica): viable alternatives in the medical treatment of benign prostatic hyperplasia and associated lower urinary tracts symptoms.  Planta Med. 2001;  67 489-500

Alexandra Paulo

Faculty of Pharmacy

University of Lisbon

Av. Prof. Gama Pinto

1649-003 Lisbon

Portugal

Fax: +351-1-7946470

Email: mapaulo@ff.ul.pt