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

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).

Key words

protein tyrosin phosphatase 1B - PTP1B - Indonesian medicinal plant - Syzygium polyanthum - Myrtaceae - daun salam - salam

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 9 Taylor SD, Hill B. Recent advances in protein tyrosine phosphatase 1B inhibitors. Expert Opin Investig Drugs 2004; 13: 199-214
• 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
• 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;
• 12 Dalimartha S. Traditional formulations for the treatment of diabetes mellitus. Jakarta: Penebar Swadaya; 2006: 89-90 [In Indonesian]
• 13 Isnandar W. A collection of 1001 Indonesian traditional prescriptions. Sidoarjo: PJ Dayang Sumbi; 2005: 25 [In Indonesian]
• 14 Arisandi Y, Andriani Y. Benefits of medicinal plants. Jakarta: Penerbit Pustaka Buku Murah; 2006: 300-301 [In Indonesian]
• 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
• 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
• 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
• 18 Cabrera GM, Seldes AM. Hydroperoxycycloartanes from Tillandsia recurvata . J Nat Prod 1995; 58: 1920-1924
• 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
• 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
• 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
• 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