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Planta Med 2004; 70(12): 1189-1194
DOI: 10.1055/s-2004-835850
Original Paper
Natural Product Chemistry
© Georg Thieme Verlag KG Stuttgart · New York

Phosphodiesterase and Thymidine Phosphorylase-Inhibiting Salirepin Derivatives from Symplocos racemosa

Muhammad Athar Abbasi1 , Viqar Uddin Ahmad1 , Muhammad Zubair1 , Naheed Fatima1 , Umar Farooq1 , Sajjad Hussain1 , Muhammad Arif Lodhi1 , M. Iqbal Choudhary1
  • 1H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi, Pakistan
Further Information

Publication History

Received: March 12, 2004

Accepted: July 24, 2004

Publication Date:
10 January 2005 (online)

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Abstract

A re-investigation of the chemical constituents of the stem bark of Symplocos racemosa Roxb. led to the isolation of four new glycosides, symplocomoside (1), symponoside (2), symplososide (3) and symploveroside (4). Benzoylsalireposide (5) and salireposide (6) were re-isolated from this plant. The structures of the new compounds were determined by 1D and 2D-homonuclear and heteronuclear NMR spectroscopy, chemical evidence, and by comparison with the published data of the closely related compounds. The glycosides 1 - 4 displayed in vitro inhibitory activity against phosphodiesterase I with IC50 values of 122 ± 0.017, 698 ± 0.06, 722 ± 0.03, 909 ± 0.09 μM, respectively. The compounds 1 - 6 also showed in vitro inhibitory activity against thymidine phosphorylase with IC50 values of 189.96 ± 1.02, 195.56 ± 2.36, 207.61 ± 1.06, 488.89 ± 4.10, 427.20 ± 5.36, 354.2 ± 5.69 μM, respectively while 1 was also found to be a urease inhibitor with an IC50 value of 54.13 ± 0.71 μM.

Key words

Symplocos racemosa - Symplocaceae - salirepin derivatives - phosphodiesterase I - thymidine phosphorylase - urease

References

  • 1 Mhaskar K S, Blatter E, Caius J F. Indian Medicinal Plants; Their usage in Ayurveda and Unani Medicines. Third revised and enlarged edition. Sri Satguru Publications Delhi; 2000 Vol. 7: pp 2087-91
    Search in Google Scholar
  • 2 Mathieu B, Rik G, Hugo C, Willy S, Cristiana S. Nucleotide pyrophosphatases/phosphodiesterases on the move.  Crit Rev Biochem Mol Biol. 2000;  35 393-432
    PubMedSearch in Google Scholar
  • 3 Razzell W E. Phosphodiesterases.  In: Methods in Enzymology. Academic Press Newark; 1963 Vol. VI: pp 236-42
    Search in Google Scholar
  • 4 Kristen J, Sanshiro H, Martin L, Kenneth P, James G, Robet T. Up-regulated expression of the phosphodiesterase nucleotide pyrophosphatase family member PC-1 is a marker and pathogenic factor for knee meniscal cartilage matrix calcification.  Arthr Rheum. 2001;  44 1071-81
    CrossrefPubMedSearch in Google Scholar
  • 5 Liekens S, Bilsen F, Clereq E D, Priego E M, Camarasa M J, Perez-Perez M J, Balzarini J. Anti-angiogenic activity of a novel multi-substrate analogue inhibitor of thymidine phosphorylase.  FEBS Lett. 2002;  510 83-8
    CrossrefPubMedSearch in Google Scholar
  • 6 Focher F, Spadari S. Thymidine phosphorylase: A two-faced Janus in anticancer chemotherapy.  Curr Cancer Drug Targets. 2001;  1 141-53
    CrossrefPubMedSearch in Google Scholar
  • 7 Mobley H L, Hausinger R P. Microbial urease: significance, regulation and molecular characterization.  Microbial Rev. 1989;  53 85-100
    PubMedSearch in Google Scholar
  • 8 Ye Q, Zhao W. New alloaromadendrane, cadinene and cyclocopacamphane type sesquiterpene derivatives and bibenzyls from Dendrobium nobile .  Planta Medica. 2002;  68 723-9
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Mamillapalli R, Haimovitz R, Ohad M, Shinitzky M. Enhancement and inhibition of snake venom phosphodiesterase activity by lysophospholipids.  FEBS Lett. 1998;  436 256-8
    CrossrefPubMedSearch in Google Scholar
  • 10 Razzell W E, Khorana H G. Studies on polynucleotides.  J Biol Chem. 1959;  234 2105-13
    PubMedSearch in Google Scholar
  • 11 Nakabayashi T, Matsuoka Y, Ikezawa H, Kimura  Y. Alkaline phosphodiesterase I release from eucaryotic plasma membranes by phosphatidylinositol-specitic phospholipase C-IV. The release from Cacia porcellus organs.  Int J Biochem. 1994;  26 171-9
    CrossrefPubMedSearch in Google Scholar
  • 12 Gomez J L, Costas M J, Ribeiro J M, Fernandez A, Romero A, Avalos M, Cameselle J C. Glycine-enhanced inhibition of rat liver nucleotide pyrophosphatase/phosphodiesterase-I by EDTA: A full account of the reported inhibition by commercial preparations of acidic fibroblast growth factor (FGF-1).  FEBS Lett. 1998;  421 77-9
    CrossrefPubMedSearch in Google Scholar
  • 13 West R A, Ledig K, Hitchings G H. British Patent 812,366; 1959.  Chem Abst. 1960;  54 592
    PubMedSearch in Google Scholar
  • 14 Krenitsky T A, Bushby S RM. Enzyme assay of thymidine phosphorylase. 1979. US Patent 4,178,212;. 1979 (Burroughs, Wellcome Co., Research Triangle Park, NC)
    Search in Google Scholar
  • 15 Sakushima A, Coskun M, Maoka T. Hydroxybenzoic acids from Boreava orientalis .  Phytochemistry. 1995;  40 257-61
    CrossrefPubMedSearch in Google Scholar
  • 16 Ahmad V U, Abbasi M A, Hussain H, Akhtar M N, Farooq U, Fatima N, Choudhary M I. Phenolic glycosides from Symplocos racemosa: natural inhibitors of phosphodiesterase I.  Phytochemistry. 2003;  63 217-20
    CrossrefPubMedSearch in Google Scholar
  • 17 Ekabo O A, Farnsworth N R, Santisuk T, Reutrakul V. Phenolic, iridoid and ionyl glycosides from Homalium ceylanicum .  Phytochemistry. 1993;  32 747-54
    CrossrefPubMedSearch in Google Scholar
  • 18 Ahmad V U, Abbasi M A, Zubair M, Fatima N, Farooq U, Choudhary M I. Phosphodiesterase-inhibiting glycosides from Symplocos racemosa .  Helv Chim Acta. 2004;  87 57-66
    CrossrefPubMedSearch in Google Scholar
  • 19 Todd M J, Hausinger R P. Competitive inhibition of Klebsiella aerogenes urease.  J Biol Chem. 1989;  264 15 835-42
    PubMedSearch in Google Scholar

Prof. Viqar Uddin Ahmad

H.E.J. Research Institute of Chemistry

International Center for Chemical Sciences

University of Karachi

Karachi-75270

Pakistan

Phone: +92-21-924-3223

Fax: +92-21-924-3190-91

Email: vuahmad@cyber.net.pk

Email: atrabbasi@yahoo.com