Citation: Li-Ping Lin, Fei-Hua Wu, Jing-Yu Liang. The first examples of ilexgenin A hybrids as a new class of multi-potent, anti-platelet agents[J]. Chinese Chemical Letters, ;2013, 24(8): 723-726. shu

The first examples of ilexgenin A hybrids as a new class of multi-potent, anti-platelet agents

Li-Ping Lin ^a,b ,
Fei-Hua Wu ^a,, ,
Jing-Yu Liang ^a,,

1.
a School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China;
2.
b Jiangsu Center for Research & Development of Medicinal Plants, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China

Corresponding author: Fei-Hua Wu, Jing-Yu Liang,
Received Date: 13 April 2013
Available Online: 6 May 2013

Seventeen novel ilexgenin A hybrids (IA-aspirin) and (IA-NO), as donor hybrids (IA-NO will release NO in vivo and function as NO donor), were designed and synthesized in order to develop new multi-targeting agents for the treatment of platelet disorders. Their in vitro activities against ADP, AA and thrombin were evaluated. As a result, IA hybrids achieved substantial increases in the three tested pathways compared with IA. Encouragingly, the most potent hybrid compounds 6d and 14d displayed about 8-fold higher potency than aspirin, and 3-fold higher potency than the simultaneous administration of aspirin and IA in inhibiting ADP-induced aggregation with IC₅₀ values of 0.15 mmol/L and 0.14 mmol/L, respectively. The results suggest these IA hybrids are good candidates for multi-target therapies, and especially, may be considered as promising ADP agonists.
- Ilexgenin A,
- Hybrids,
- Multi-potent anti-platelet activity,
- ADP agonists
1. [1]
  [1] S. Yusuf, S. Reddy, S. Ounpuu, S. Anand, Global burden of cardiovascular diseases. Part I: General considerations, the epidemiologic transition, risk factors, and impact of urbanization, Circulation 104 (2001) 2746-2753.
2. [2]
  [2] M.J. Davies, A.C. Thomas, Plaque fissuring -the cause of acutemyocardial infarction, sudden ischaemic death and crescendo angina, Br. Heart J. 53 (1985) 363-373.
3. [3]
  [3] V. Fuster, L. Badimon, J.J. Badimon, J.H. Chesebro, The pathogenesis of coronary artery disease and the acute coronary syndromes, N. Engl. J. Med. 326 (1992) 242-250.
4. [4]
  [4] H. Yang, G.Y. Hu, J. Chen, Y. Wang, Z.H. Wang, Synthesis, resolution, and antiplatelet activity of 3-substituted 1(3H)-isobenzofuranone, Bioorg. Med. Chem. Lett. 17 (2007) 5210-5213.
5. [5]
  [5] L.A. Urbano, J. Bogousslavsky, Antiplatelet drugs in ischemic stroke prevention: from monotherapy to treatment, Cerebrovasc. Dis. 17 (2004) 74-80.
6. [6]
  [6] G. Micieli, A. Cavallini, New therapeutic strategies with antiplatelet agents, Neurol. Sci. 25 (2004) S13-S15.
7. [7]
  [7] (a) Y.N. Han, S.K. Baik, T.H. Kim, B.H. Han, Antithrombotic activities of saponins from Ilex pubescens, Arch. Pharm. Res. 10 (1987) 115-120;
8. [8]
  (b) D.K. Lee, H.S. Lee, M.D. Huh, et al., Antiplatelet action of Ilexoside D, a triterpenoid saponin from Ilex pubescens, Arch. Pharm. Res. 14 (1991) 352-356;
9. [9]
  (c) Y.N. Han, J.I. Song, I.K. Rhee, Anticoagulant activity of Ilexoside D, a triterpenoid saponin from Ilex pubescens, Arch. Pharm. Res. 16 (1993) 209-212.
10. [10]
  [8] B.Q. Li, N.G. Li, F. Feng, Y.P. Tang, J.A. Duan, Synthesis and anti-platelet aggregation activities of ferulic acid esters, J. China Pharm. Univ. 40 (2009) 486-490.
11. [11]
  [9] (a) Y. Li, X.L. Wang, R. Fu, et al., Synthesis and evaluation of nitric oxide-releasing derivatives of 3-n-butylphthalide as anti-platelet agents, Bioorg. Med. Chem. Lett. 21 (2011) 4210-4214;
12. [12]
  (b) Z.L. Min, Y.H. Zhang, P. Zhuang, et al., Synthesis and anti-platelet activities of nitric-oxide releasing derivatives of 3-butylphthalide, J. China Pharm. Univ. 39 (2008) 392-397.
13. [13]
  [10] C. Patrono, B. Coller, J.E. Dalen, Platelet-active drugs: the relationships among dose, effectiveness, and side effects, Chest 119 (Suppl. 1) (2001) 39S-63S.
14. [14]
  [11] P.G. Wang, M. Xian, X.P. Tang, et al., Nitric oxide donors: chemical activities and biological applications, Chem. Rev. 102 (2002) 1091-1134.
15. [15]
  [12] G.V.R. Born, M.J. Cross, The aggregation of blood platelets, J. Physiol. 168 (1963) 178-195.
16. [16]
  [13] Antiplatelet aggregation assays: Blood samples were withdrawn from rat abdominal aorta and mixed with 3.8% trisodium citrate (9:1, v/v), followed by centrifuging at 1000 rpm for 10 min. The supernatants were collected and used as platelet rich plasma (PRP). Additional sample were centrifuged at 3000 rpm for 10 min and the supernatants were collected as platelet poor plasma (PPP). The effect of individual compounds on the AA, ADP and thrombin-induced platelet aggregation was measured by the Born's turbidimetric method using a Platelet-Aggregometer (LBY-NJ Platelet-Aggregometer, Beijing). Briefly, PRP (280 mL) was pre-treated in duplicated with vehicle (0.5% DMSO), different concentrations of individual compounds or the reference drugs and exposed to 10 mL of AA (final concentration 40 μmol/L), ADP (final concentration 10 μmol/L) or thrombin (final concentration 5 U/mL) incubated at 37 ℃ for 5 min. Changes in the light transmittance of the reaction mixture were continuously recorded for 5 min and the maximal aggregation was also recorded. The anti-platelet aggregation activity of tested compound was evaluated as inhibition rate (%) which was determined using the following formula: Inhibition rate (%) = (1 the maximal aggregation of compound/the maximal aggregation of control)×100.
17. [17]
  [14] P. Theroux, Antiplatelet therapy: do the new platelet inhibitors add significantly to the clinical benefits of aspirin? Am. Heart J. 134 (1997) s62-s70.
18. [18]
  [15] J.B. Li, Z. Jian, L. Huang, et al., Comparison of collagen vs adenosine diphosphate in detecting antiplatelet effect in patients with coronary artery disease, Biomed. Pharm. 63 (2009) 608-612.
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