Protein Tyrosine Phosphatase 1B (PTP1B)-Inhibiting Constituents from the Leaves of Syzygium polyanthum

 

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Abstract

A methanol extract of the leaves of Syzygium polyanthum (Wight) Walp. afforded four new acylbenzene derivatives (1–4) together with seven known compounds (5–11). The structures of 1–11 were elucidated by extensive spectroscopic methods and comparison with the literature data. The new compounds 1–3 and a known compound, campest-4-en-3-one (10), exhibited a significant protein tyrosine phosphatase 1B inhibitory activity with IC₅₀ values of 13.1 ± 0.1, 5.77 ± 0.15, 4.01 ± 0.26, and 10.4 ± 0.5 µM, respectively. The inhibitory potency of the new compounds 2 and 3 was comparable to that of a positive control RK-682 (IC₅₀, 5.51 ± 0.04 µM).

• References

• 1 Byon JCH, Kusari AB, Kusari J. Protein-tyrosine phosphatase-1B acts as a negative regulator of insulin signal transduction. Mol Cell Biochem 1998; 182: 101-108
  CrossrefPubMedGoogle Scholar
• 2 Ahmad F, Li PM, Meyerovitch J, Goldstein BJ. Osmotic loading of neutralizing antibodies demonstrates a role for protein-tyrosine phosphatase 1B in negative regulation of the insulin action pathway. J Biol Chem 1995; 270: 20503-20508
  CrossrefPubMedGoogle Scholar
• 3 Elchebly M, Payette P, Michaliszyn E, Cromlish W, Collins S, Loy AL, Normandin D, Cheng A, Himms-Hagen J, Chan CC, Ramachandran C, Gresser MJ, Tremblay ML, Kennedy BP. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science 1999; 283: 1544-1548
  CrossrefPubMedGoogle Scholar
• 4 Haj FG, Zabolotny JM, Kim YB, Kahn BB, Neel BG. Liver-specific protein-tyrosine phosphatase 1B (PTP1B) re-expression alters glucose homeostasis of PTP1B–/– mice. J Biol Chem 2005; 280: 15038-15046
  CrossrefPubMedGoogle Scholar
• 5 Zabolotny JM, Bence-Hanulec KK, Stricker-Krongrad A, Haj F, Wang Y, Minokoshi Y, Kim YB, Elmquist JK, Tartaglia LA, Kahn BB, Neel BG. PTP1B regulates leptin signal transduction in vivo . Dev Cell 2002; 2: 489-495
  CrossrefPubMedGoogle Scholar
• 6 Bence KK, Delibegovic M, Xue B, Gorgun CZ, Hotamisligil GS, Neel BG, Kahn BB. Neuronal PTP1B regulates body weight, adiposity and leptin action. Nat Med 2006; 12: 917-924
  CrossrefPubMedGoogle Scholar
• 7 Liu G, Trevillyan JM. Protein tyrosine phosphatase 1B as a target for the treatment of impaired glucose tolerance and type II diabetes. Curr Opin Investig Drugs 2002; 3: 1608-1616
  PubMedGoogle Scholar
• 8 Zhang YZ, Lee SY. PTP1B inhibitors as potential therapeutics in the treatment of type 2 diabetes and obesity. Expert Opin Investig Drugs 2003; 12: 223-233
  CrossrefPubMedGoogle Scholar
• 9 Taylor SD, Hill B. Recent advances in protein tyrosine phosphatase 1B inhibitors. Expert Opin Investig Drugs 2004; 13: 199-214
  CrossrefPubMedGoogle Scholar
• 10 Combs AP. Recent advances in the discovery of competitive protein tyrosine phosphatase 1B inhibitors for the treatment of diabetes, obesity, and cancer. J Med Chem 2010; 53: 2333-2344
  CrossrefPubMedGoogle Scholar
• 11 Saifudin A, Kadota S, Tezuka Y. Protein tyrosine phosphatase 1B inhibitory activity of Indonesian herbal medicines and constituents of Cinnamomum burmanii and Zingiber aromaticum . J Nat Med advance online publication 30.05.2012; DOI: 10.1007/s11418-012-0674-7.
  PubMedGoogle Scholar
• 12 Dalimartha S. Traditional formulations for the treatment of diabetes mellitus. Jakarta: Penebar Swadaya; 2006: 89-90 [In Indonesian]
  Google Scholar
• 13 Isnandar W. A collection of 1001 Indonesian traditional prescriptions. Sidoarjo: PJ Dayang Sumbi; 2005: 25 [In Indonesian]
  Google Scholar
• 14 Arisandi Y, Andriani Y. Benefits of medicinal plants. Jakarta: Penerbit Pustaka Buku Murah; 2006: 300-301 [In Indonesian]
  Google Scholar
• 15 Hasan MS, Ahmed MI, Mondal S, Uddin SJ, Masud MM, Sadhu SK, Ishibashi M. Antioxidant, antinociceptive activity and general toxicity study of Dendrophthoe falcate and isolation of quercitrin as the major component. Orient Pharm Exp Med 2006; 6: 355-360
  CrossrefPubMedGoogle Scholar
• 16 Uomori A, Nakagawa Y, Yoshimatsu S, Seo S, Sankawa U, Takeda K. Biosynthesis of campesterol and dihydrobrassicasterol in cultured cells of Amsoniaelliptica . Phytochemistry 1992; 31: 156
  PubMedGoogle Scholar
• 17 Seto H, Fujioka S, Takatsuto S, Koshino H, Shimizu T, Yoshid S. Synthesis of 6-oxy functionalized campest-4-en-3-ones: efficient hydroperoxidation at C-6 of campest-5-en-3-one with molecular oxygen and silica gel. Steroids 2000; 65: 443-449
  CrossrefPubMedGoogle Scholar
• 18 Cabrera GM, Seldes AM. Hydroperoxycycloartanes from Tillandsia recurvata . J Nat Prod 1995; 58: 1920-1924
  CrossrefPubMedGoogle Scholar
• 19 Korulʼkina IM, Shulʼts EE, Zhusupova GE, Abilov ZA, Erzhanov KB, Chahudri MI. Biologically active compounds from Limonium gmelinii and L. popovii . Chem Nat Compd 2004; 40: 465-471
  CrossrefPubMedGoogle Scholar
• 20 Kijima H, Otsuka H, Ide T, Ogimi C, Hirata E, Takushi A, Takeda Y. Glycosides of megastigmane and of the simple alcohols from Alangium premnifolium . Phytochemistry 1996; 42: 723-727
  CrossrefPubMedGoogle Scholar
• 21 Hoang DM, Ngoc TM, Dat NT, Ha DT, Kim YH, Luong HV, Ahn JS, Bae KH. Protein tyrosine phosphatase 1B inhibitors isolated from Morus bombycis . Bioorg Med Chem Lett 2009; 19: 6759-6761
  CrossrefPubMedGoogle Scholar
• 22 Hamaguchi T, Sudo T, Osada H. RK-682, a potent inhibitor of tyrosine phosphatase, arrested the mammalian cell cycle progression at G₁ phase. FEBS Lett 1995; 372: 54-58
  CrossrefPubMedGoogle Scholar

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