Click-chemistry-derived triazole ligands of arginine-glycine-aspartate (RGD) integrins with a broad capacity to inhibit adhesion of melanoma cells and both in vitro and in vivo angiogenesis

Journal of Medicinal Chemistry

Volumn 53, Issue 19, 2010, Pages 7119-7128

  Trabocchi, Andrea ^a   Menchi, Gloria ^a   Cini, Nicoletta ^a,b   Bianchini, Francesca ^a,b   Raspanti, Silvia ^a,b   Bottoncetti, Anna ^a,b   Pupi, Alberto ^a,b   Calorini, Lido ^a,b   Guarna, Antonio ^a  

^a UNIVERSITY OF FLORENCE   (Italy)

^b ISTITUTO TOSCANO TUMORI   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

3 [2 (4 GUANIDINOETHYL[1,2,3]TRIAZOL 1 YL)ACETYLAMINO] 3 PHENYLPROPIONIC ACID; 3 [2 (4 GUANIDINOMETHYL[1,2,3]TRIAZOL 1 YL)ACETYLAMINO] 3 PHENYLPROPIONIC ACID; 3 [2 [4 (2 GUANIDINOETHYL)[1,2,3]TRIAZOL 1 YL]ACETYLAMINO] 3 PHENYLPROPIONIC ACID; 3 [2 [4 (3 GUANIDINOPROPYL)[1,2,3]TRIAZOL 1 YL]ACETYLAMINO] 3 PHENYLPROPIONIC ACID; 3 [2 [4 (4 CARBAMIMIDOYLPIPERAZIN 1 YLMETHYL)[1,2,3]TRIAZOL 1 YL]ACETYLAMINO] 3 PHENYLPROPIONIC ACID; 3 [2 [4 [2 (4 CARBAMIMIDOYLPIPERAZIN 1 YL)ETHYL][1,2,3]TRIAZOL 1 YL]ACETYLAMINO)] 3 PHENYLPROPIONIC ACID; 3 [2 [4 [2 (4 CARBAMIMIDOYLPIPERAZIN 1 YL)ETHYL][1,2,3]TRIAZOL 1 YL]ACETYLAMINO] 3 PHENYLPROPIONIC ACID; ALKYNE; ALPHA5 INTEGRIN; ANTINEOPLASTIC AGENT; ARGININE; ARGINYLGLYCYLASPARTIC ACID; ARGINYLGLYCYLASPARTIC ACID MIMETIC; ASPARTIC ACID; AZIDE; BETA3 INTEGRIN; COPPER; FIBRONECTIN; GLYCINE; INTEGRIN; LIGAND; PEPTIDOMIMETIC AGENT; PYRROLE DERIVATIVE; TRIAZOLE; TYROSINE; UNCLASSIFIED DRUG; VITRONECTIN; [[2 (4 GUANIDINOMETHYL[1,2,3]TRIAZOL 1 YL)ACETYL]PHENYLAMINO]ACETIC ACID; [[2 [4 (2 GUANIDINOETHYL)[1,2,3]TRIAZOL 1 YL]ACETYL]PHENYLAMINO]ACETIC ACID; [[2 [4 (3 GUANIDINOPROPYL)[1,2,3]TRIAZOL 1 YL]ACETYL]PHENYLAMINO]ACETIC ACID; [[2 [4 [2 (4 CARBAMIMIDOYLPIPERAZIN 1 YL)ETHYL][1,2,3]TRIAZOL 1 YL]ACETYL]PHENYLAMINO]ACETIC ACID; 3-(2-(4-(3-GUANIDINOPROPYL)(1,2,3)TRIAZOL-1-YL)ACETYLAMINO)-3-PHENYLPROPIONIC ACID; ALPHAVBETA5 INTEGRIN; ANGIOGENESIS INHIBITOR; ARGINYL-GLYCYL-ASPARTIC ACID; OLIGOPEPTIDE; PHENYLPROPIONIC ACID DERIVATIVE; PROTEIN BINDING; SCLEROPROTEIN; TRIAZOLE DERIVATIVE; VITRONECTIN RECEPTOR;

ANGIOGENESIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; BINDING AFFINITY; BIOASSAY; CATALYSIS; CELL ADHESION; CONTROLLED STUDY; EXPERIMENTAL MODEL; EXTRACELLULAR MATRIX; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; MELANOMA CELL; MOLECULAR MODEL; NONHUMAN; PROTEIN BINDING; ANIMAL; C57BL MOUSE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECTS; DRUG SCREENING; ENDOTHELIUM CELL; MELANOMA; METABOLISM; MOLECULAR MIMICRY; MOUSE; NEOVASCULARIZATION, PATHOLOGIC; PATHOLOGY; PHYSIOLOGY; RADIOASSAY; STEREOISOMERISM; STRUCTURE ACTIVITY RELATION; SYNTHESIS; TUMOR CELL LINE; VASCULARIZATION;

ALKYNES; ANGIOGENESIS INHIBITORS; ANIMALS; AZIDES; CELL ADHESION; CELL LINE, TUMOR; DRUG SCREENING ASSAYS, ANTITUMOR; ENDOTHELIAL CELLS; EXTRACELLULAR MATRIX PROTEINS; HUMANS; INTEGRIN ALPHAVBETA3; LIGANDS; MELANOMA; MICE; MICE, INBRED C57BL; MODELS, MOLECULAR; MOLECULAR MIMICRY; NEOVASCULARIZATION, PATHOLOGIC; OLIGOPEPTIDES; PHENYLPROPIONATES; PROTEIN BINDING; RADIOLIGAND ASSAY; RECEPTORS, VITRONECTIN; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TRIAZOLES;

EID: 77957926274     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100754z     Document Type: Article

References (58)

1. For reviews, see the following: Arnaout, M. A.; Goodman, S. L.; Xiong, J. P. Coming to grips with integrin binding to ligands Curr. Opin. Cell Biol. 2002, 14, 641-651
2. Hynes, R. O. Integrins: bidirectional, allosteric signaling machines Cell 2002, 110, 673-687
3. Plow, E. F.; Haas, T. A.; Zhang, L.; Loftus, J.; Smith, J. W. Ligand binding to integrins J. Biol. Chem. 2000, 275, 21785-21788
4. Humphries, M. J. Integrin structure Biochem. Soc. Trans. 2000, 28, 311-339
5. Ruoslathi, E.; Pierschbacher, M. D. New perspectives in cell adhesion: RGD and integrins Science 1987, 238, 491-497
6. 3, see the following: Eliceiri, B. P.; Cheresh, D. A. Role of αv integrins during angiogenesis Cancer J. 2000, 13, 245-249
7. 3 integrin receptor synergizes with radioimmunotherapy to increase efficacy and apoptosis in breast cancer xenografts Cancer Res. 2002, 62, 4263-4272
8. 5, see the following: Marinelli, L.; Gottschalk, K. E.; Meyer, A.; Novellino, E.; Kessler, H. Human integrin αvβ5: homology modeling and ligand binding J. Med. Chem. 2004, 47, 4166-4177
9. Friedlander, M.; Theesfeld, C. L.; Sugita, M.; Fruttiger, M.; Thomas, M. A.; Chang, S.; Cheresh, D. Involvement of integrins alpha v beta 3 and alpha v beta 5 in ocular neovascular diseases. A Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 9764-9769
10. Friedlander, M.; Brooks, P. C.; Shaffer, R. W.; Kincaid, C. M.; Varner, J. A.; Cheresh, D. A. Definition of two angiogenic pathways by distinct alpha v integrins Science 1995, 270, 1500-1502
11. Mitjans, F.; Meyer, T.; Fittschen, C.; Goodman, S.; Jonczyk, A.; Marshall, J. F.; Reyes, G.; Piulats, J. In vivo therapy of malignant melanoma by means of antagonists of alphav integrins Int. J. Cancer 2000, 87, 716-723
12. MacDonald, T. J.; Taga, T.; Shimada, H.; Tabrizi, P.; Zlokovic, B. V.; Cheresh, D. A.; Laug, W. E. Preferential susceptibility of brain tumors to the antiangiogenic effects of an alpha 31(v) integrin antagonist Neurosurgery 2001, 48, 151-157
13. Albelda, S. M.; Mette, S. A.; Elder, D. E.; Stewart, R.; Damjanovich, L.; Herlyn, M.; Buck, C. A. Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression Cancer Res. 1990, 50, 6757-6764
14. Van Belle, P. A.; Elenitsas, R.; Satyamoorthy, K.; Wolfe, J. T.; Guerry, D., IV; Schuchter, L.; Van Belle, T. J.; Albelda, S.; Tahin, P.; Herlyn, M.; Elder, D. E. Progression-related expression of beta3 integrin in melanomas and nevi Hum. Pathol. 1999, 30, 562-567
15. Seftor, R. E. Role of the beta3 integrin subunit in human primary melanoma progression: multifunctional activities associated with alpha(v)beta3 integrin expression Am. J. Pathol. 1998, 153, 1347-1351
16. McGary, E. C.; Lev, D. C.; Bar-Eli, M. Cellular adhesion pathways and metastatic potential of human melanoma Cancer Biol. Ther. 2002, 1, 459-465
17. Hofmann, U. B.; Westphal, J. R.; Waas, E. T.; Becker, J. C.; Ruiter, D. J.; van Muijen, G. N. Coexpression of integrin alpha(v)beta3 and matrix metalloproteinase-2 (MMP-2) coincides with MMP-2 activation: correlation with melanoma progression J. Invest. Dermatol. 2000, 115, 625-632
18. 3 antagonism Anti-Cancer Agents Med. Chem. 2006, 6, 407-428
19. Kerbel, R.; Folkman, J. Clinical translation of angiogenesis inhibitors Nat. Rev. Cancer. 2002, 2, 727-739
20. Folkman, J. Angiogenesis: an organizing principle for drug discovery? Nat. Rev. Drug Discovery 2007, 6, 273-286 (Pubitemid 46505878)
21. Brooks, P. C.; Stromblad, S.; Klemke, R.; Visscher, D.; Sarkar, F. H.; Cheresh, D. A. The role of αv integrins during angiogenesis: insights into potential mechanisms of action and clinical development J. Clin. Invest. 1995, 96, 1815-1822
22. Kumar, C. C.; Malkowski, M.; Yin, Z.; Tanghetti, E.; Yaremko, B.; Nechuta, T.; Varner, J.; Liu, M.; Smith, E. M.; Neustadt, B.; Presta, M.; Armstrong, L. Cancer Res. 2001, 61, 2232-2238
23. 3 antagonist using structure-based drug design Eur. J. Med. Chem. 2007, 42, 334-343
24. 3 dual antagonists Bioorg. Med. Chem. 2006, 14, 2109-2130 (Pubitemid 43254729)
25. 3 antagonists: recent developments Curr. Med. Chem. 2005, 12, 51-70
26. Bach, A. C., II; Espina, J. R.; Jackson, S. A.; Stouten, P. F. W.; Duke, J. L.; Mousa, S. A.; DeGrado, W. F. Type II- to type I β-turn swap changes specificity for integrins J. Am. Chem. Soc. 1996, 118, 293-294
27. Dechantsreiter, M.; Plnaker, E.; Mathä, B.; Lohof, E.; Hölzemann, G.; Jonczyk, A.; Goodman, S. L.; Kessler, H. N-Methylated cyclic RGD peptides as highly active and selective αvβ3 integrin antagonists J. Med. Chem. 1999, 42, 3033-3040
28. v-selective RGD peptides Angew. Chem., Int. Ed. 2000, 39, 2761-2764
29. Belvisi, L.; Bernardi, A.; Checchia, A.; Manzoni, L.; Potenza, D.; Scolastico, C.; Castorina, M.; Capelli, A.; Giannini, G.; Carminati, P.; Pisano, C. Potent integrin antagonists from a small library of RGD-including cyclic pseudopeptides Org. Lett. 2001, 3, 1001-1004
30. 5 integrin dual binders J. Med. Chem. 2005, 48, 7675-7687
31. Belvisi, L.; Bernardi, A.; Colombo, M.; Manzoni, L.; Potenza, D.; Scolastico, C.; Giannini, G.; Marcellini, M.; Riccioni, T.; Castorina, M.; Lo Giudice, P.; Carminati, P.; Pisano, C. Targeting integrins: insights into structure and activity of cyclic RGD pentapeptide mimics containing azabicycloalkane amino acids Bioorg. Med. Chem. 2006, 14, 169-180
32. For reviews, see the following: Arkin, M. R.; Wells, J. A. Small-molecule inhibitors of protein-protein interactions: progressing towards the dream Nat. Rev. Drug Discovery 2004, 3, 301-317
33. Szczepankiewicz, B. G.; Liu, G.; Jajduk, P. J.; Abad-Zapatero, C.; Pei, Z.; Xin, Z.; Lubben, T. H.; Trevillyan, J. M.; Stashko, M. A.; Ballaron, S. J.; Liang, H.; Huang, F.; Hutchings, C. W.; Fesik, S. W.; Jirousek, M. R. Discovery of a potent, selective protein tyrosine phosphatase 1B inhibitor using a linked-fragment strategy J. Am. Chem. Soc. 2003, 125, 4087-4096 (Pubitemid 36512302)
34. Erlanson, D. A.; Braisted, A. C.; Raphael, D. R.; Randal, M.; Stroud, R. M.; Gordon, E. M.; Wells, J. Site-directed ligand discovery Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 9367-9372
35. Birk, A.; Lin, Y.-C.; Elder, J.; Wong, C.-H. A quick diversity-oriented amide-forming reaction to optimize P-subsite residues of HIV protease inhibitors Chem. Biol. 2002, 9, 891-896
36. Kolb, H. C.; Sharpless, K. B. The growing impact of click chemistry on drug discovery Drug Discovery Today 2003, 8, 1128-1137
37. Wu, C. -Y.; Jan, J.-T.; Ma, S.-H.; Kuo, C.-J.; Juan, H.-F.; Cheng, Y.-S. E.; Hsu, H.-H.; Huang, H.-C.; Wu, D.; Brik, A.; Liang, F.-S.; Liu, R.-S.; Fang, J.-M.; Chen, S.-T.; Liang, P.-H.; Wong, C.-H. Small molecules targeting severe acute respiratory syndrome human coronavirus Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 10012-10017
38. Wu, C.-Y.; Chang, C.-F.; Chen, J. S.-Y.; Wong, C.-H. Rapid diversity-oriented synthesis in microtiter plates for in situ screening: discovery of potent and selective α-fucosidase inhibitors Angew. Chem., Int. Ed. 2003, 42, 4661-4664
39. Best, M. D.; Birk, A.; Chapman, E.; Lee, L. V.; Cheng, W.-C.; Wong, C.-H. Rapid discovery of potent sulfotransferase inhibitors by diversity-oriented reaction in microplates followed by in situ screening ChemBioChem 2004, 5, 811-819
40. Lee, L. V.; Mitchell, M. L.; Huang, S.-J.; Fokin, V. V.; Sharpless, K. B.; Wong, C.-H. A potent and highly selective inhibitor of human α-1,3-fucosyltransferase via click chemistry J. Am. Chem. Soc. 2003, 125, 9588-9589
41. Belkin, V. M.; Belkin, A. M.; Koteliansky, V. E. Human smooth muscle VLA-1 integrin: purification, substrate specificity, localization in aorta, and expression during development J. Cell Biol. 1990, 111, 2159-2170
42. Pytela, R.; Pierschbacher, M. D.; Argraves, S.; Suzuki, S.; Ruoslahti, E. Arginine-glycine-aspartic acid adhesion receptors Methods Enzymol. 1987, 144, 475-489
43. Kumar, C. C.; Malkowski, M.; Yin, Z.; Tanghetti, E.; Yaremko, B.; Nechuta, T.; Varner, J.; Liu, M.; Smith, E. M.; Neustadt, B.; Presta, M.; Armstrong, L. Inhibition of angiogenesis and tumor growth by SCH221153, a dual alpha(v)beta3 and alpha(v)beta5 integrin receptor antagonist Cancer Res. 2001, 61, 2232-2238
44. 3 receptor J. Pharmacol. Exp. Ther. 1997, 283, 843-853
45. Dijkgraaf, I.; Kruijtzer, J. A.; Frielink, C.; Soede, A. C.; Hilbers, H. W.; Oyen, W. J.; Corstens, F. H.; Liskamp, R. M.; Boerman, O. C. Synthesis and biological evaluation of potent alphavbeta3-integrin receptor antagonists Nucl. Med. Biol. 2006, 33, 953-961
46. 5 integrin binders embedding 4-aminoproline residues J. Med. Chem. 2008, 51, 1771-1782
47. Takagi, J.; Petre, B. M.; Walz, T.; Springer, T. A. Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling Cell 2002, 110, 599-611
48. Humphries, M. J.; McEwan, P. A.; Barton, S. J.; Buckley, P. A.; Bella, J.; Mould, A. P. Integrin structure: heady advances in ligand binding, but activation still makes the knees wobble Trends Biochem. Sci. 2003, 28, 313-320
49. Shimaoka, M.; Springer, T. A. Therapeutic antagonists and conformational regulation of integrin function Nat. Rev. Drug Discovery 2003, 2, 703-716
50. Xiong, J. P.; Stehle, T.; Zhang, R.; Joachimiak, A.; Frech, M.; Goodman, S. L.; Arnaout, M. A. Crystal structure of the extracellular segment of integrin v3 in complex with an Arg-Gly-Asp ligand Science 2002, 296, 151-155
51. Bednar, R. A.; Gaul, S. L.; Hamill, T. G.; Egbertson, M. S.; Shafer, J. A.; Hartman, G. D.; Gould, R. J.; Bednar, B. Identification of low molecular weight GP IIb/IIIa antagonists that bind preferentially to activated platelets J. Pharmacol. Exp. Ther. 1998, 285, 1317-1326
52. Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Belew, R. K.; Olson, A. J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function J. Comput. Chem. 1998, 19, 1639-1662
53. Autodock results were processed using the PyMOL software: DeLano, W. L. The PyMOL Molecular Graphics System, version 0.99; DeLano Scientific LLC: San Carlos, CA; http://www.pymol.org.
54. Li, L.; Price, J. E.; Fan, D.; Zhang, R. D.; Bucana, C. D.; Fidler, I. J. Correlation of growth capacity of human tumor cells in hard agarose with their in vivo proliferative capacity at specific metastatic sites J. Natl. Cancer Inst. 1989, 81, 1406-1412
55. Shattil, S. J.; Kim, C.; Ginsberg, M. H. The final step of integrin activation: the end game Nat. Rev. Mol. Cell Biol. 2010, 11, 288-300
56. Wai, P. Y.; Kuo, P. C. Osteopontin: regulation in tumor metastasis Cancer Metastasis Rev. 2008, 27, 103-118
57. Kumar, C. C.; Nie, H.; Armstrong, L.; Zhang, R.; Vijay-Kumar, S.; Tsarbopoulos, A. FEBS Lett. 1998, 429, 239-248
58. Khalili, P.; Arakelian, A.; Chen, G.; Plunkett, M. L.; Beck, I.; Parry, G. C.; Do'ate, F.; Shaw, D. E.; Mazar, A. P.; Rabbani, S. A. A non-RGD-based integrin binding peptide (ATN-161) blocks breast cancer growth and metastasis in vivo Mol. Cancer Ther. 2006, 5, 2271-2280