1,8-naphthalimide derivatives: new leads against dynamin i gtpase activity · 2015. 6. 16. ·...
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1,8-Naphthalimide derivatives: New leads against dynamin I GTPase activity
Mohammed K. Abdel-Hamid, Kylie A. Macgregor, Luke R. Odell, Ngoc Chau, Anna Mariana, Ainslie Whiting, Phillip J Robinson and Adam McCluskey
Supplementary Data
1. Figure S1. Clustering of the 1,8-naphthalimide scaffold (stick representation) at the GTP binding pocket of dynI (ribbon representation) 2. Calculated Ligand Efficiencies and related physicochemical properties of key napthaladyn and other dynamin inhibitor compounds. 3. 1H and 13C NMR spectra of key analogues
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2015
Figure S1. Clustering of the 1,8-naphthalimide scaffold (stick representation) at the GTP binding pocket of dynI (ribbon representation)
Table S1. Calculated ligand efficiencies and related physicochemical properties of key napthaladyn and other dynamin inhibitor compounds. The values cLogP and PSA were calculated using the Osiris Molecular Property Explorer (http://www.organic-chemistry.org/prog/peo/).
Compound Class Structure MW HAC cLogP* PSA (Å2)
HBA HBD IC50 (µM)
Ligand Efficiency
Ref
Napthaladyn 23
388.39 25 -1.59 163.4 7 4 19.1 0.20 This work
Napthaladyn 29
464.49 31 0.18 163.4 7 4 18.5 0.16 This work
MiTMAB
336.39 19 2.79 - - - 3.1 0.31 1
Bis-T-22
464.45 35 1.47 186.7 8 6 1.7 0.16 2
Dynole 2-24
408.58 30 5.23 20.2 2 1 0.56 0.23 3
Dyngo-4a
338.31 25 3.01 122.3 6 5 0.35 0.26 4
NO O
NH2
SO3K
OH
O
NO O
SO3KNH2
CO2H
NBr
HO
HOCN
NH
O
NH
O
CN
OH
OH
NH2
N
NH
N
OH
NH
ON
OH
OHOH
Rhodadyn C10
350.0 23 1.89 90.17 5 0 7.0 0.22 5
Anti-psychotic - Trifluoperazine
407.50 28 4.93 35.02 3 0 2.6 0.20 6
SSRI - Seralin
306.23 20 4.2 12.03 1 1 7.3 0.26 7
* Calculated as the SO3H analogue;
References:
1. T. A. Hill, L. R. Odell, A. Quan, G. Ferguson, P. J. Robinson, A. McCluskey. Long chain amines and long chain ammonium salts as novel inhibitors of dynamin GTPase activity. Bioorg. Med. Chem. Lett., 2004, 14, 3275-3278
2. T. Hill, L. R. Odell, J. K. Edwards, M. E. Graham, A. B. McGeachie, J. Rusak, A. Quan, R. Abagyan, J. L. Scott, P. J. Robinson, A. McCluskey. Small molecule inhibitors of dynamin I GTPase activity: development of dimeric tyrphostins. J. Med. Chem., 2005, 48, 7781-7788
3. C. P. Gordon, B. Venn-Brown, M. J. Robertson, K. A. Young, N. Chau, A. Quan, P. J. Robinson, A. McCluskey. Development of second generation indole based dynamin GTPase inhibitors. J. Med. Chem., 2013, 56, 46-59.
4. A. McCluskey, J. A. Daniel, G. Hadzic, N. Chau, E. L. Clayton, A. Mariana, A. Whiting, J. Lloyd, A. Quan, L. Moshkanbaryans, S. Perera, M. Chircop, A. B. McGeachie, M. T. Howes, R. G. Parton, M. Campbell, J. A. Sakoff, X. Wang, J. –Y. Sun, M. J. Robertson, F. M. Deane, T. H. Nguyen, F. A. Meunier, M. A. Cousin, P. J. Robinson. Building a better dynasore: The dyngos potently inhibit dynamin and endocytosis. Traffic 2013, 14, 1272-1289
5. M. J. Robertson, G. Hadzic, J. Ambrus, D. Y. Pome, E. Hyde, A. Whiting, A. Mariana, L. von Kleist, N. Chau, V. Haucke, P. J. Robinson, A. McCluskey. The rhodadynsTM – novel inhibitors of dynamin GTPase. ACS Med. Chem. Lett., 2012, 3, 352-356
ONS
N
O
S
N
S
N
N
F3C
HN
ClCl
6. J. A. Daniel, N. Ngoc Chau, A. Whiting, L. von Kleist, P. Maamary, M. K. Abdel-Hamid, V. Haucke, A. McCluskey, P. J. Robinson. Phenothiazine-derived antipsychotic drugs inhibit dynamin and clathrin-mediated endocytosis. Traffic, 2015, 14, 1272-1289.
7. M. Otomo, K. Takahashi, H. Miyoshi, K. Osada, H. Nakashima, N. Yamagichi. Some Selective Serotonin Reuptake Inhibitors Inhibit Dynamin I Guanosine Triphosphatase (GTPase), Biol. Pharm. Bull. 2008, 31, 1489-1495.
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