Pyrimidyn compounds: Dual-action small molecule pyrimidine-based dynamin inhibitors

ACS Chemical Biology

Volumn 8, Issue 7, 2013, Pages 1507-1518

  McGeachie, Andrew B ^a,f   Odell, Luke R ^b,g   Quan, Annie ^a   Daniel, James A ^a   Chau, Ngoc ^a   Hill, Timothy A ^b,h   Gorgani, Nick N ^a   Keating, Damien J ^d   Cousin, Michael A ^d   Van Dam, Ellen M ^c   Mariana, Anna ^b   Whiting, Ainslie ⁱ   Perera, Swetha ^a   Novelle, Aimee ^a   Young, Kelly A ^b   Deane, Fiona M ^b   Gilbert, Jayne ^e   Sakoff, Jennette A ^e   Chircop, Megan ^a   McCluskey, Adam ^b   Robinson, Phillip J ^a   more..

^a UNIVERSITY OF SYDNEY   (Australia)

^b UNIVERSITY OF NEWCASTLE   (Australia)

^c GARVAN INSTITUTE OF MEDICAL RESEARCH   (Australia)

^d FLINDERS UNIVERSITY   (Australia)

^e CALVARY MATER NEWCASTLE HOSPITAL   (Australia)

^f NEUROSCIENCE RESEARCH AUSTRALIA   (Australia)

^g UPPSALA UNIVERSITY   (Sweden)

^h UNIVERSITY OF QUEENSLAND   (Australia)

ⁱ NONE

Author keywords

[No Author keywords available]

Indexed keywords

DYNAMIN; DYNAMIN I; DYNAMIN II; GUANOSINE TRIPHOSPHATE; PHOSPHOLIPID; PYRIMIDINE DERIVATIVE; PYRIMIDYN; TRANSFERRIN; UNCLASSIFIED DRUG;

ARTICLE; CELL CYCLE; CONTROLLED STUDY; CYTOTOXICITY; DRUG DESIGN; DRUG INHIBITION; DRUG MECHANISM; DRUG STRUCTURE; ENDOCYTOSIS; IN VITRO STUDY; NERVE ENDING; PRIORITY JOURNAL; PROTEIN LIPID INTERACTION; PROTEIN LOCALIZATION; QUANTITATIVE ANALYSIS; SYNAPTIC VESICLE ENDOCYTOSIS;

ANIMALS; BIOLOGICAL ASSAY; BLOTTING, WESTERN; CERCOPITHECUS AETHIOPS; COS CELLS; DRUG DESIGN; DYNAMINS; ENDOCYTOSIS; FLOW CYTOMETRY; MOLECULAR STRUCTURE; PROTEIN BINDING; PYRIMIDINES; SMALL MOLECULE LIBRARIES;

EID: 84880557627     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/cb400137p     Document Type: Article

References (71)

1. McMahon, H. T. and Boucrot, E. (2011) Molecular mechanism and physiological functions of clathrin-mediated endocytosis Nat. Rev. Mol. Cell. Biol. 12, 517-533
2. Liu, J. P. and Robinson, P. J. (1995) Dynamin and endocytosis Endocr. Rev. 16, 590-607
3. Conner, S. D. and Schmid, S. L. (2003) Regulated portals of entry into the cell Nature 422, 37-44
4. Ferguson, S. M. and De Camilli, P. (2012) Dynamin, a membrane-remodelling GTPase Nat. Rev. Mol. Cell. Biol. 11, 75-88
5. Hinshaw, J. E. (2000) Dynamin and its role in membrane fission Annu. Rev. Cell Dev. Biol. 16, 483-519
6. Cousin, M. A. and Robinson, P. J. (2001) The dephosphins: Dephosphorylation by calcineurin triggers synaptic vesicle endocytosis Trends Neurosci. 24, 659-665
7. Muhlberg, A. B., Warnock, D. E., and Schmid, S. L. (1997) Domain structure and intramolecular regulation of dynamin GTPase EMBO J. 16, 6676-6683
8. Sever, S., Muhlberg, A. B., and Schmid, S. L. (1999) Impairment of dynamin's GAP domain stimulates receptor-mediated endocytosis Nature 398, 481-486
9. Scaife, R., Venien-Bryan, C., and Margolis, R. L. (1998) Dual function C-terminal domain of dynamin-1: modulation of self-assembly by interaction of the assembly site with SH3 domains Biochemistry 37, 17673-17679
10. Graham, M. E., Anggono, V., Bache, N., Larsen, M. R., Craft, G. E., and Robinson, P. J. (2007) The in vivo phosphorylation sites of rat brain dynamin I J. Biol. Chem. 282, 14695-14707
11. Anggono, V., Smillie, K. J., Graham, M. E., Valova, V. A., Cousin, M. A., and Robinson, P. J. (2006) Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosis Nat. Neurosci. 9, 752-760
12. Praefcke, G. J. and McMahon, H. T. (2004) The dynamin superfamily: universal membrane tubulation and fission molecules? Nat. Rev. Mol. Cell. Biol. 5, 133-147
13. Vallis, Y., Wigge, P., Marks, B., Evans, P. R., and McMahon, H. T. (1999) Importance of the pleckstrin homology domain of dynamin in clathrin-mediated endocytosis Curr. Biol. 9, 257-260
14. Achiriloaie, M., Barylko, B., and Albanesi, J. P. (1999) Essential role of the dynamin pleckstrin homology domain in receptor-mediated endocytosis Mol. Cell. Biol. 19, 1410-1415
15. Ramachandran, R., Pucadyil, T. J., Liu, Y. W., Acharya, S., Leonard, M., Lukiyanchuk, V., and Schmid, S. L. (2009) Membrane insertion of the pleckstrin homology domain variable loop 1 is critical for dynamin-catalyzed vesicle scission Mol. Biol. Cell 20, 4630-4639
16. Roux, A., Uyhazi, K., Frost, A., and De Camilli, P. (2006) GTP-dependent twisting of dynamin implicates constriction and tension in membrane fission Nature 441, 528-531
17. Marks, B., Stowell, M. H., Vallis, Y., Mills, I. G., Gibson, A., Hopkins, C. R., and McMahon, H. T. (2001) GTPase activity of dynamin and resulting conformation change are essential for endocytosis Nature 410, 231-235
18. Morlot, S., Galli, V., Klein, M., Chiaruttini, N., Manzi, J., Humbert, F., Dinis, L., Lenz, M., Cappello, G., and Roux, A. (2012) Membrane shape at the edge of the dynamin helix sets location and duration of the fission reaction Cell 151, 619-629
19. Ivanov, A. I. (2008) Pharmacological inhibition of endocytic pathways: is it specific enough to be useful? Methods Mol. Biol. 440, 15-33
20. Atwood, W. J. (2001) A combination of low-dose chlorpromazine and neutralizing antibodies inhibits the spread of JC virus (JCV) in a tissue culture model: Implications for prophylactic and therapeutic treatment of progressive multifocal leukencephalopathy J. Neurovirol. 7, 307-310
21. Gray, J. A., Sheffler, D. J., Bhatnagar, A., Woods, J. A., Hufeisen, S. J., Benovic, J. L., and Roth, B. L. (2001) Cell-type specific effects of endocytosis inhibitors on 5-hydroxytryptamine2A receptor desensitization and resensitization reveal an arrestin-, GRK2-, and GRK5-independent mode of regulation in human embryonic kidney 293 cells Mol. Pharmacol. 60, 1020-1030
22. Davies, P. J., Cornwell, M. M., Johnson, J. D., Reggianni, A., Myers, M., and Murtaugh, M. P. (1984) Studies on the effects of dansylcadaverine and related compounds on receptor-mediated endocytosis in cultured cells Diabetes Care 7 (Suppl 1) 35-41
23. Larkin, J. M., Brown, M. S., Goldstein, J. L., and Anderson, R. G. (1983) Depletion of intracellular potassium arrests coated pit formation and receptor-mediated endocytosis in fibroblasts Cell 33, 273-285
24. Lindgren, C. A., Emery, D. G., and Haydon, P. G. (1997) Intracellular acidification reversibly reduces endocytosis at the neuromuscular junction J. Neurosci. 17, 3074-3084
25. Wang, L.-H., Rothberg, K. G., and Anderson, R. G. (1993) Mis-assembly of clathrin lattices on endosomes reveals a regulatory switch for coated pit formation J. Cell Biol. 123, 1107-1117
26. von Kleist, L., Stahlschmidt, W., Bulut, H., Gromova, K., Puchkov, D., Robertson, M. J., MacGregor, K. A., Tomilin, N., Pechstein, A., Chau, N., Chircop, M., Sakoff, J., von Kreis, J., Saenger, W., Krausslich, H. G., Shupliakov, O., Robinson, P. J., McCluskey, A., and Haucke, V. (2011) Role of the clathrin terminal domain in regulating coated pit dynamics revealed by small molecule inhibition Cell 146, 471-484
27. Harper, C. B., Popoff, M. R., McCluskey, A., Robinson, P. J., and Meunier, F. A. (2012) Targeting membrane trafficking in infection prophylaxis: dynamin inhibitors Trends Cell Biol. 23, 90-101
28. Hill, T. A., Odell, L. R., Quan, A., Abagyan, R., Ferguson, G., Robinson, P. J., and McCluskey, A. (2004) Long chain amines and long chain ammonium salts as novel inhibitors of dynamin GTPase activity Bioorg. Med. Chem. Lett. 14, 3275-3278
29. Zhang, J., Lawrance, G. A., Chau, N., Robinson, P. J., and McCluskey, A. (2008) From Spanish fly to room temperature ionic liquids (RTILs): Synthesis, thermal stability and inhibition of dynamin 1 GTPase by a novel class of RTILs New J. Chem. 32, 28-36
30. Hill, T. A., Gordon, C. P., McGeachie, A. B., Venn-Brown, B., Odell, L. R., Chau, N., Quan, A., Mariana, A., Sakoff, J. A., Chircop, M., Robinson, P. J., and McCluskey, A. (2009) Inhibition of dynamin mediated endocytosis by the dynoles-synthesis and functional activity of a family of indoles J. Med. Chem. 52, 3762-3773
31. Gordon, C. P., Venn-Brown, B., Robertson, M. J., Young, K. A., Chau, N., Mariana, A., Whiting, A. E., Chircop, M., Robinson, P. J., and McCluskey, A. (2013) Development of second generation indole based dynamin GTPase inhibitors J. Med. Chem. 56, 46-59
32. Hill, T. A., Mariana, A., Gordon, C. P., Odell, L. R., McGeachie, A. B., Chau, N., Daniel, J. A., Gorgani, N. N., Robinson, P. J., and McCluskey, A. (2010) Iminochromene inhibitors of dynamin I & II GTPase activity and endocytosis J. Med. Chem. 53, 4094-4102
33. Odell, L. R., Howan, D., Gordon, C. P., Robertson, M. J., Chau, N., Mariana, A., Whiting, A. E., Abagyan, R., Daniel, J. A., Gorgani, N. N., Robinson, P. J., and McCluskey, A. (2010) The pthaladyns: GTP competitive inhibitors of dynamin I and II GTPase derived from virtual screening J. Med. Chem. 53, 5267-5280
34. Robertson, M. J., Hadzic, G., Ambrus, J., Hyde, E., Yuri Pomè, D., Chau, N., Whiting, A. E., Robinson, P. J., and McCluskey, A. (2012) The Rhodadyn series, a new class of small molecule inhibitors of dynamin GTPase activity ACS Med. Chem. Lett. 3, 352-356
35. Harper, C. B., Martin, S., Nguyen, T. H., Daniels, S. J., Lavidis, N. A., Popoff, M. R., Hadzic, G., Mariana, A., Chau, N., McCluskey, A., Robinson, P. J., and Meunier, F. A. (2011) Dynamin inhibition blocks botulinum neurotoxin type-A endocytosis in neurons and delays botulism J. Biol. Chem. 286, 35966-35976
36. Macia, E., Ehrlich, M., Massol, R., Boucrot, E., Brunner, C., and Kirchhausen, T. (2006) Dynasore, a cell-permeable inhibitor of dynamin Dev. Cell 10, 839-850
37. Quan, A., McGeachie, A. B., Keating, D. J., van Dam, E. M., Rusak, J., Chau, N., Malladi, C. S., Chen, C., McCluskey, A., Cousin, M. A., and Robinson, P. J. (2007) MiTMAB is a surface-active dynamin inhibitor that blocks endocytosis mediated by dynamin I or dynamin II Mol. Pharmacol. 72, 1425-1439
38. Ertl, P., Jelfs, S., Muhlbacher, J., Schuffenhauer, A., and Selzer, P. (2006) Quest for the rings. In silico exploration of ring universe to identify novel bioactive heteroaromatic scaffolds J. Med. Chem. 49, 4568-4573
39. Herman, B. D., Votruba, I., Holy, A., Sluis-Cremer, N., and Balzarini, J. (2010) The acyclic 2,4-diaminopyrimidine nucleoside phosphonate acts as a purine mimetic in HIV-1 reverse transcriptase DNA polymerization J. Biol. Chem. 285, 12101-12108
40. Lawrence, H. R., Martin, M. P., Luo, Y., Pireddu, R., Yang, H., Gevariya, H., Ozcan, S., Zhu, J. Y., Kendig, R., Rodriguez, M., Elias, R., Cheng, J. Q., Sebti, S. M., Schonbrunn, E., and Lawrence, N. J. (2012) Development of o-chlorophenyl substituted pyrimidines as exceptionally potent aurora kinase inhibitors J. Med. Chem. 55, 7392-7416
41. Robinson, P. J., Sontag, J.-M., Liu, J. P., Fykse, E. M., Slaughter, C., McMahon, H. T., and Südhof, T. C. (1993) Dynamin GTPase regulated by protein kinase C phosphorylation in nerve terminals Nature 365, 163-166
42. Marks, B. and McMahon, H. T. (1998) Calcium triggers calcineurin- dependent synaptic vesicle recycling in mammalian nerve terminals Curr. Biol. 8, 740-749
43. Quan, A. and Robinson, P. J. (2005) Rapid purification of native dynamin I and colorimetric GTPase assay Methods Enzymol. 404, 556-569
44. Chappie, J. S., Acharya, S., Leonard, M., Schmid, S. L., and Dyda, F. (2010) G domain dimerization controls dynamin's assembly-stimulated GTPase activity Nature 465, 435-440
45. Ogay, I. D., Lihoradova, O. A., Azimova, S., Abdukarimov, A. A., Slack, J. M., and Lynn, D. E. (2006) Transfection of insect cell lines using polyethylenimine Cytotechnology 51, 89-98
46. van der Bliek, A. M., Redelmeier, T. E., Damke, H., Tisdale, E. J., Meyerowitz, E. M., and Schmid, S. L. (1993) Mutations in human dynamin block an intermediate stage in coated vesicle formation J. Cell Biol. 122, 553-563
47. Dunkley, P. R., Jarvie, P. A., and Robinson, P. J. (2008) A rapid Percoll gradient procedure for preparation of synaptosomes Nat. Protoc. 3, 1718-1728
48. 2+ inhibition of dynamin arrests synaptic vesicle recycling at the active zone J. Neurosci. 20, 949-957
49. Daniel, J. A., Malladi, C. S., Kettle, E., McCluskey, A., and Robinson, P. J. (2012) Analysis of synaptic vesicle endocytosis in synaptosomes by high content screening Nat. Protoc. 7, 1439-1455
50. Joshi, S., Gaddipati, S., Gilbert, J., Smith, C. M., Mariana, A., Gordon, C. P., Sakoff, J. A., McCluskey, A., Robinson, P. J., Braithwaite, A. W., and Chircop, M. (2010) The dynamin inhibitors MiTMAB and OcTMAB induce cytokinesis failure and inhibit cell proliferation in human cancer cells Mol. Cancer Ther. 9, 1995-2006
51. Stevens, D. R., Schirra, C., Becherer, U., and Rettig, J. (2011) Vesicle pools: lessons from adrenal chromaffin cells Front. Synaptic Neurosci. 3, 2
52. Keller, P. A., Kirkwood, K., Morgan, J., Westcott, S., and McCluskey, A. (2003) The prevention of preterm labour-corticotropin releasing hormone type 1 receptors as a target for drug design and development Mini-Rev. Med. Chem. 3, 295-303
53. Keller, P. A., Bowman, M., Dang, K. H., Garner, J., Leach, S. P., Smith, R., and McCluskey, A. (1999) Pharmacophore development for corticotropin- releasing hormone: new insights into inhibitor activity J. Med. Chem. 42, 2351-2357
54. McCluskey, A., Keller, P. A., Morgan, J., and Garner, J. (2003) Synthesis, molecular modeling and biological activity of methyl and thiomethyl substituted pyrimidines as corticotropin releasing hormone type 1 antagonists Org. Biomol. Chem. 1, 3353-3361
55. Hill, T. A., Odell, L. R., Edwards, J. K., Graham, M. E., McGeachie, A. B., Rusak, J., Quan, A., Abagyan, R., Scott, J. L., Robinson, P. J., and McCluskey, A. (2005) Small molecule inhibitors of dynamin I GTPase activity: Development of dimeric tyrphostins J. Med. Chem. 48, 7781-7788
56. Robinson, P. J., Rusak, J., Quan, A., Hill, T. A., McGeachie, A. B., McCluskey, A., and Cousin, M. A. Inhibition of dynamin by bis-tyrphostin suggests two roles for GTPase activity in synaptic vesicle endocytosis. Traffic 1901, submitted
57. Zheng, J., Cahill, S. M., Lemmons, M. A., Fushman, D., Schlessinger, J., Cowburn, D., and Lemmon, M. A. (1996) Identification of the binding site for acidic phospholipids on the PH domains of dynamin: implications for stimulation of GTPase activity J. Mol. Biol. 255, 14-21
58. Lin, H. C., Barylko, B., Achiriloaie, M., and Albanesi, J. P. (1997) Phosphatidylinositol (4,5)-bisphosphate-dependent activation of dynamins I and II lacking the proline/arginine-rich domains J. Biol. Chem. 272, 25999-26004
59. Stowell, M. H., Marks, B., Wigge, P., and McMahon, H. T. (1999) Nucleotide-dependent conformational changes in dynamin: evidence for a mechanochemical molecular spring Nat. Cell Biol. 1, 27-32
60. Scurlock, J. E. and Curtis, B. M. (1981) Tetraethylammonium derivatives: ultralong-acting local anesthetics? Anesthesiology 54, 265-269
61. Schreier, S. and Malheiros, S. V. (2000) de Paula, E. Surface active drugs: self-association and interaction with membranes and surfactants. Physicochemical and biological aspects Biochim. Biophys. Acta 1508, 210-234
62. Chircop, M., Perera, S., Mariana, A., Lau, H., Ma, M. P. C., Gilbert, J., Jones, N. C., Gordon, C. P., Young, K. A., Morokoff, A., Sakoff, J., O'Brien, T. J., McCluskey, A., and Robinson, P. J. (2011) Inhibition of dynamin by dynole 34-2 induces cell death following cytokinesis failure in cancer cells Mol Cancer Ther 10, 1553-1562
63. Joshi, S., Braithwaite, A. W., Robinson, P. J., and Chircop, M. (2011) Dynamin inhibitors induce caspase-mediated apoptosis following cytokinesis failure in human cancer cells and this is blocked by Bcl-2 overexpression Mol. Cancer 10, 78
64. Schmid, S. L. and Frolov, V. A. (2011) Dynamin: Functional design of a membrane fission catalyst Annu. Rev. Cell Dev. Biol. 27, 79-105
65. Lee, A., Frank, D. W., Marks, M. S., and Lemmon, M. A. (1999) Dominant-negative inhibition of receptor-mediated endocytosis by a dynamin-1 mutant with a defective pleckstrin homology domain Curr. Biol. 9, 261-264
66. Ferguson, S. M., Brasnjo, G., Hyashi, M., Wolfel, M., Collesi, C., Giovedi, S., Raimondi, A., Gong, L. W., Areil, P., Paradise, S., O'Toole, E., Flavell, R., Cremona, O., Miesenbock, G., Ryan, T. A., and De Camilli, P. (2007) A selective activity-dependent requirement for dynamin 1 in synaptic vesicle endocytosis Science 316, 570-574
67. Raimondi, A., Ferguson, S. M., Lou, X., Armbruster, M., Paradise, S., Giovedi, S., Messa, M., Kono, N., Takasaki, J., Cappello, V., O'Toole, E., Ryan, T. A., and De Camilli, P. (2011) Overlapping role of dynamin isoforms in synaptic vesicle endocytosis Neuron 70, 1100-1114
68. Samasilp, P., Chan, S. A., and Smith, C. (2012) Activity-dependent fusion pore expansion regulated by a calcineurin-dependent dynamin-syndapin pathway in mouse adrenal chromaffin cells J. Neurosci. 32, 10438-10447
69. Reid, A. T., Lord, T., Stranger, S. J., Roman, S. D., McCluskey, A., Robinson, P. J., Aitken, R. J., and Nixon, B. (2012) Dynamin regulates specific membrane fusion events necessary for acrosomal exocytosis in mouse spermatozoa J. Biol. Chem. 287, 37659-37672
70. Anantharam, A., Bittner, M. A., Aikman, R. L., Stuenkel, E. L., Schmid, S. L., Axelrod, D., and Holz, R. W. (2011) A new role for the dynamin GTPase in the regulation of fusion pore expansion Mol. Biol. Cell 22, 1907-1918
71. Chircop, M., Malladi, C. S., Lian, A., Page, S. L., Zavortink, M., Gordon, C. P., McCluskey, A., and Robinson, P. J. (2010) Calcineurin activity is required for the completion of cytokinesis Cell. Mol. Life Sci. 67, 3725-3737