Limitations of conventional anticoagulant therapy and the promises of non-heparin based conformational activators of antithrombin

Journal of Thrombosis and Thrombolysis

Volumn 34, Issue 2, 2012, Pages 251-259

  Rashid, Qudsia ^a   Singh, Poonam ^a   Abid, Mohammad ^a   Jairajpuri, Mohamad Aman ^a  

^a JAMIA MILLIA ISLAMIA CENTRAL UNIVERSITY   (India)

Author keywords

Antithrombin; Coagulation; Flavonoids; Heparin; Serine protease inhibitor

Indexed keywords

ANTICOAGULANT AGENT; ANTITHROMBIN; ANTIVITAMIN K; BENZOFURAN 6AS; BENZOFURAN DERIVATIVE; BLOOD CLOTTING FACTOR 10A; BLOOD CLOTTING FACTOR 10A INHIBITOR; CHONDROITIN SULFATE; DIOSMIN HEXASULFATE; FLAVONOID; FONDAPARINUX; HEPARIN; LIGNIN; LOW MOLECULAR WEIGHT HEPARIN; MANGIFERIN HEPTASULFATE; PENTASACCHARIDE; POLYMER; QUERCETIN 3 ACETYL 7,3',4' TRISULFATE; QUERCETIN 3,7,3',4' TETRASULFATE; TETRAHYDROISOQUINOLINE DERIVATIVE; TETRAHYDROISOQUINOLINE IAS5; THROMBIN; THROMBIN INHIBITOR; UNCLASSIFIED DRUG; WARFARIN; XANTHONE DERIVATIVE;

ALLOSTERISM; ANAPHYLAXIS; ANTICOAGULANT THERAPY; ARTICLE; BINDING AFFINITY; BLEEDING; CONFORMATIONAL TRANSITION; DRUG BIOAVAILABILITY; DRUG CONTAMINATION; DRUG FATALITY; DRUG MONITORING; DRUG POTENCY; DRUG STRUCTURE; HEART ATRIUM FIBRILLATION; HEMOSTASIS; HEPARIN INDUCED THROMBOCYTOPENIA; HUMAN; HYPOTENSION; INTERNATIONAL NORMALIZED RATIO; LIVER TOXICITY; OSTEOPOROSIS; PRIORITY JOURNAL; PROTHROMBIN TIME; SKIN NECROSIS; THROMBIN TIME; THROMBOCYTOPENIC PURPURA; THROMBOGENESIS; THROMBOSIS; VEIN THROMBOSIS;

ANTICOAGULANTS; ANTITHROMBIN III; ATRIAL FIBRILLATION; FACTOR XA; HEPARIN; HUMANS; PROTEIN CONFORMATION; VENOUS THROMBOSIS;

EID: 84865123079     PISSN: 09295305     EISSN: 1573742X     Source Type: Journal    
DOI: 10.1007/s11239-012-0712-z     Document Type: Article

References (73)

1. Corral J, Vincete V, Carrell RW (2005) Thrombosis as a conformational disease. Haematologica 90(2):238-246 (Pubitemid 40293287)
2. Rand MD, Lock JB, Veer CV, Gaffney DP, Mann KG (1996) Blood clotting in minimally altered whole blood. Blood 88(9):3432-3445 (Pubitemid 26365577)
3. Furie B, Furie BC (2008) Mechanisms of thrombus formation. N Engl J Med 28(9):938-949
4. Rosendaal FR (2005) Venous thrombosis: the role of genes, environment, and behavior hematology. Am Soc Hematol Educ Progam 1:1-12
5. Rebecca Jensen (2002) Clinical presentation of arterial thrombosis vs. venous thrombosis. Clin Hemost Rev 16(8):1-6
6. Lippi G, Franchini M, Targher G (2011) Arterial thrombus formation in cardiovascular disease. Nat Rev Cardiol 8(9):502-512
7. Reistma PH, Rosendaal R (2007) Past and future of genetic research in thrombosis. J Thromb Haemost 1:264-269
8. Husmann M, Barton M (2007) Therapeutical potential of direct thrombin inhibitors for atherosclerotic vascular disease. Expert Opin Investig Drugs 16(5):563-567 (Pubitemid 46723266)
9. Agnelli G, Sonaglia F (1999) Clinical status of direct thrombin inhibitors. Crit Rev Oncol Hematol 31(2):97-117 (Pubitemid 29333753)
10. Fareed J, Hoppensteadt DA, Bick RL (2000) An update on heparins at the beginning of the new millennium. Semin Thromb Hemost 26(Suppl 1):5-21
11. Hoffman M, Monroe DM (2007) Coagulation 2006: a modern view of hemostasis. Hematol Oncol Clin North Am 21(1):1-11 (Pubitemid 46135905)
12. Mann KG, Brummel K, Butenas S (2003) What is all that thrombin for? J Thromb Haemost 1(7):1504-1514
13. Liu L, Ma H, Yang N, Tang Y, Guo J, Tao W, Duan J (2010) A series of natural flavonoids as thrombin inhibitors: structureactivity relationships. Thromb Res 126(5):e365-e378
14. Turpie AG (2007) Oral, direct factor Xa inhibitors in development for the prevention and treatment of thromboembolic diseases. Arterioscler Thromb Vasc Biol 27(6):1238-1247 (Pubitemid 46809411)
15. Desai UR (2004) New antithrombin-based anticoagulants. Med Res Rev 24(2):151-181 (Pubitemid 38230678)
16. Brambel CE (1955) The role of flavonoids in coumarin anticoagulant therapy. Ann NY Acad Sci 61(3):678-681
17. Hirsh J (1991) Oral anticoagulant drugs. N Engl J Med 324(26):1865-1875
18. Chan YC, Valenti D, Mansfield AO, Stansby G (2000) Warfarin induced skin necrosis. Br J Surg 87(3):266-272 (Pubitemid 30156350)
19. Eikelboom JW, Weitz JI (2010) New anticoagulants. Circulation 121(13):1523-1532
20. Gray E, Mulloy B, Barrowcliffe TW (2008) Heparin and lowmolecular- weight heparin. Thromb Haemost 99(5):807-818
21. Rabenstein DL (2002) Heparin and heparan sulfate: structure and function. Nat Prod Rep 19(3):312-331 (Pubitemid 34656777)
22. Lefkou E, Khamashta M, Hampson G, Hunt BJ (2010) Review: low-molecular-weight heparin induced osteoporosis and osteoporotic fractures: a myth or an existing entity? Lupus 19(1):3-12
23. Januzzi JL Jr, Jang IK (2000) Fundamental concepts in the pathobiology of heparin-induced thrombocytopenia. J Thromb Thrombolysis 10(Suppl 1):7-11
24. Liu H, Zhang Z, Linhardt RJ (2009) Lessons learned from the contamination of heparin. Nat Prod Rep 26(3):313-321
25. Correia-da-Silva M, Sousa E, Duarte B, Marques F, Carvalho F, Cunha-Ribeiro LM, Pinto MM (2011) Polysulfated xanthones: multipathway development of a new generation of dual anticoagulant/antiplatelet agents. J Med Chem 54(15):5373-5384
26. Raghuraman A, Liang A, Krishnasamy C, Lauck T, Gunnarsson GT, Desai UR (2009) On designing non-saccharide, allosteric activators of antithrombin. Eur J Med Chem 44(6):2626-2631
27. Henry BL, Connell J, Liang A, Krishnasamy C, Desai UR (2009) Interaction of antithrombin with sulfated, low molecular weight lignins: opportunities for potent, selective modulation of antithrombin function. J Biol Chem 284(31):20897-20908
28. Janin S, Meneveau N, Mahemuti A, Descotes-Genon V, Dutheil J, Chopard R, Seronde MF, Schiele F, Bernard Y, Bassand JP (2009) Safety and efficacy of fondaparinux as an adjunctive treatment to thrombolysis in patients with high and intermediate risk pulmonary embolism. J Thromb Thrombolysis 28(3):320-324
29. Weitz JI, Hirsh J, Samama MM, American College of Chest Physicians (2008) New antithrombotic drugs: American College of Chest Physicians evidence-based clinical practice guidelines (8th ed.). Chest 133(Suppl 6):234S-256S (Pubitemid 351892968)
30. Gandhi NS, Mancera RL (2008) The structure of glycosaminoglycans and their interactions with proteins. Chem Biol Drug Des 72(6):455-482
31. Capila I, Linhardt RJ (2002) Heparin-protein interactions. Angew Chem Int Ed Engl 41(3):391-412
32. Marciniak E, Gockerman JP (1977) Heparin-induced decrease in circulating antithrombin III. Lancet 2(8038):581-584 (Pubitemid 8176606)
33. Knot EA, de Jong E, ten Cate JW, Gie LK, van Royen EA (1987) Antithrombin III: biodistribution in healthy volunteers. Thromb Haemost 58(4):1008-1011
34. Carrell RW, Pemberton PA, Boswell DR (1987) The serpins: evolution and adaptation in a family of protease inhibitors. Cold Spring Harb Symp Quant Biol 52:527-535 (Pubitemid 18262363)
35. Olson ST, Bjork I (1994) Regulation of thrombin activity by antithrombin and heparin. Semin Thromb Hemost 20(4):373-409 (Pubitemid 24381849)
36. Olson ST, Bjork I, Sheffer R, Craig PA, Shore JD, Choay J (1992) Role of the antithrombin-binding pentasaccharide in heparin acceleration of antithrombin-proteinase reactions. Resolution of the antithrombin conformational change contribution to heparin rate enhancement. J Biol Chem 267(18):12528-12538
37. Wright HT, Scarsdale JN (1995) Structural basis for serpin inhibitor activity. Proteins 22(3):210-225
38. Lindahl U, Backkstrom G, Thunberg L, Leder IG (1980) Evidence for a 3-O-sulfated D glucosamine residue in the antithrombin- binding sequence of heparin. Proc Natl Acad Sci USA 77(11):6551-6555 (Pubitemid 11219166)
39. Carrell RW, Stein PE, Fermi G, Wardell MR (1994) Biological implications of a 3A structure of dimeric antithrombin. Structure 2(4):257-270
40. Olson ST, Shore JD (1981) Binding of high affinity heparin to antithrombin III. Characterization of the protein fluorescence enhancement. J Biol Chem 256(21):11065-11072 (Pubitemid 12181590)
41. Gettins PG (2002) Serpin structure, mechanism, and function. Chem Rev 102(12):4751-4804
42. Belzar KJ, Zhou A, Carrell RW, Gettins PG, Huntington JA (2002) Helix D elongation and allosteric activation of antithrombin. J Biol Chem 277(10):8551-8558 (Pubitemid 34968319)
43. Meagher JL, Olson ST, Gettins PG (2000) Critical role of the linker region between helix D and strand 2A in heparin activation of antithrombin. J Biol Chem 275(4):2698-2704 (Pubitemid 30082039)
44. Izaguirre G, Zhang W, Swanson R, Bedsted T, Olson ST (2003) Localization of an antithrombin exosite that promotes rapid inhibition of factors Xa and IXa dependent on heparin activation of the serpin. J Biol Chem 278(51):51433-51440 (Pubitemid 38020383)
45. Carrell RW, Evans DLI, Stein H (1991) Mobile reactive centre of serpins and the control of thrombosis. Nature 353(6344):576-579
46. Carrell RW, Perry DJ (1996) The unhinged antithrombins. Br J Haematol 93(2):253-257 (Pubitemid 26148729)
47. Jin L, Abrahams J-P, Skinner R, Petitou M, Pike RN, Carrell RW (1997) The anticoagulant activation of antithrombin by heparin. Proc Natl Acad Sci USA 94(26):14683-14688 (Pubitemid 28041434)
48. van Boeckel CAA, Grootenhuis PDJ, Visser A (1994) A mechanism for heparin induced potentiation of antithrombin III. Nat Struct Biol 1(7):423-425
49. Jairajpuri MA, Lu A, Desai U, Olson ST, Bjork I, Bock SC (2003) Antithrombin III phenylalanines 122 and 121 contribute to its high affinity for heparin and its conformational activation. J Biol Chem 278(18):15941-15950 (Pubitemid 36799712)
50. Desai UR, Petitou M, Bjork I, Olson ST (1998) Mechanism of heparin activation of antithrombin. Role of individual residues of the pentasaccharide activating sequence in the recognition of native and activated states of antithrombin. J Biol Chem 273(13):7478-7487 (Pubitemid 28152771)
51. Petitou M, van Boeckel CA (2004) A synthetic antithrombin III binding pentasaccharide is now a drug! What comes next? Angew Chem Int Ed Engl 43(24):3118-3133 (Pubitemid 39257600)
52. Correia-da-Silva M, Sousa E, Duarte B, Marques F, Carvalho F, Cunha-Ribeiro LM, Pinto MM (2011) Flavonoids with an oligopolysulfated moiety: a new class of anticoagulant agents. J Med Chem 54(1):95-106
53. Gunnarsson GT, Desai UR (2002) Interaction of designed sulfated flavanoids with antithrombin: lessons on the design of organic activators. J Med Chem 45(20):4460-4470
54. Gunnarsson GT, Desai UR (2003) Exploring new non-sugar sulfated molecules as activators of antithrombin. Bioorg Med Chem Lett 13(4):679-683 (Pubitemid 36298467)
55. Guglielmone HA, Agnese AM, Nunez SC, Cabrera JL (2002) Anticoagulant effect and action mechanism of sulphated flavonoids from Flaveria bidentis. Thromb Res 105(2):183-188 (Pubitemid 34214936)
56. Gunnarsson GT, Riaz M, Adams J, Desai UR (2005) Synthesis of per-sulfated flavonoids using 2,2,2-trichloroethyl protecting group and their factor Xa inhibition potential. Bioorg Med Chem 13(5):1783-1789 (Pubitemid 40215264)
57. Rimbach G, Weinberg PD, de Pascual-Teresa S, Alonso MG, Ewins BA, Turner R, Minihane AM, Botting N, Fairley B, Matsugo S, Uchida Y, Cassidy A (2004) Sulfation of genistein alters its antioxidant properties and its effect on platelet aggregation and monocyte and endothelial function. Biochim Biophys Acta 1670(3):229-237 (Pubitemid 38229773)
58. Liang A, Thakkar JN, Desai UR (2010) Study of physicochemical properties of novel highly sulfated, aromatic, mimetics of heparin and heparan sulfate. J Pharm Sci 99(3):1207-1216
59. Verghese J, Liang A, Sidhu PPS, Hindle M, Zhou Q, Desai UR (2009) First steps toward synthetic, allosteric, direct inhibitors of thrombin and factor Xa. Bioorg Med Chem Lett 19(15):4126-4129
60. Monien BH, Henry BL, Raghuraman A, Hindle M, Desai UR (2006) Novel chemo-enzymatic oligomers of cinnamic acids as direct and indirect inhibitors of coagulation proteinases. Bioorg Med Chem 14(23):7988-7998 (Pubitemid 44584706)
61. Pietta PG (2000) Flavonoids as antioxidants. J Nat Prod 63(7):1035-1042
62. Janssen K, Mensink RP, Cox FJ, Harryvan JL, Hovenier R, Hollman PC, Katan MB (1998) Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study. Am J Clin Nutr 67(2):255-262 (Pubitemid 28076717)
63. Lale A, Herbert JM, Augereau JM, Billon M, Leconte M, Gleye J (1996) Ability of different flavonoids to inhibit the procoagulant activity of adherent human monocytes. J Nat Prod 59(3):273-276 (Pubitemid 26111101)
64. Wu QL, Wang SP, Du LJ, Zhang SM, Yang JS, Xiao PG (1998) Chromone glycosides and flavonoids from Hypericum japonicum. Phytochemistry 49(5):1417-1420
65. LiuW, SongZJ, LiangNC, She J,MoLE(1999) Inhibitory effects of sodium Quercetin monosulfate on pig platelet aggregation induced by thrombin. Zhongguo Yao Li Xue Bao 20(7):623-626 (Pubitemid 29344056)
66. Liu W, Liang NC (2000) Inhibitory effect of disodium quercetin- 7,40-disulfate on aggregation of pig platelets induced by thrombin and its mechanism. Acta Pharmacol Sin 21(8):737-741 (Pubitemid 30626466)
67. HA,AgneseAM, NunezMontoya SC, Cabrera JL (2005) Inhibitory effects of sulphated flavonoids isolated from Flaveria bidentis on platelet aggregation. Thromb Res 115(6):495-502 (Pubitemid 40409983)
68. Gunnarsson GT, Desai UR (2004) Hydropathic interaction analyses of small organic activators binding to antithrombin. Bioorg Med Chem 12(3):633-640 (Pubitemid 38102233)
69. Gunnarsson GT, Desai UR (2002) Designing small, nonsugar activators of antithrombin using hydropathic interaction analyses. J Med Chem 45(6):1233-1243 (Pubitemid 34263560)
70. Kuntic V, Filipovic I, Vujic Z (2011) Effects of rutin and hesperidin and their Al(III) and Cu(II) complexes on in vitro plasma coagulation assays. Molecules 16(2):1378-1388
71. Monien BH, Desai UR (2005) Antithrombin activation by nonsulfated, non-polysaccharide organic polymer. J Med Chem 48(4):1269-1273 (Pubitemid 40270472)
72. Monien BH, Cheang KI, Desai UR (2005) Mechanism of poly(acrylic acid) acceleration of antithrombin inhibition of thrombin: implications for the design of novel heparin mimics. J Med Chem 48(16):5360-5368 (Pubitemid 41113920)
73. Olson ST, Bjork I, Bock SC (2002) Identification of critical molecular interactions mediating heparin activation of antithrombin: implications for the design of improved heparin anticoagulants. Trends Cardiovasc Med 12(5):198-205 (Pubitemid 34823629)