D. Rambabu et al. / Bioorg. Med. Chem. Lett. 23 (2013) 1351–1357
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Table 5
Docking scores obtained after docking compounds 3k, 3n and 3g into SIRT1 protein
Molecules
Dock scorea
Steric
Protein desolvation
Ligand desolvation H-bond
Clash
Ligand desolvation
Hydrogen bond
Splitomicin
ꢀ9.9
ꢀ7.6
ꢀ7.9
ꢀ7.3
ꢀ13.9
ꢀ17.4
ꢀ17.0
ꢀ17.6
ꢀ3.9
7.5
6.0
ꢀ0.1
ꢀ0.9
ꢀ0.8
ꢀ0.8
0.2
0.9
0.8
0.9
0.3
3.6
4.1
3.8
ꢀ0.3
ꢀ1.4
ꢀ1.1
ꢀ1.5
3k
3n
3g
7.76
a
FRED Chemgauss4 score.
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Figure 7. Binding mode and orientation of 3k, 3n and 3g in hSIRT-1 catalytic
pocket. Surface area colored in grey represents the hydrophobic property and blue
the hydrophilic property.
Acknowledgments
12. Krüger, K.; Tillack, A.; Beller, M. Adv. Synth. Catal. 2008, 350, 2153.
13. Ackermann, L. Synlett 2007, 507.
14. For a review, see: Pal, M. Synlett 2009, 2896.
The authors thank management of ILS for encouragement and
support. D.H. and M.P. thank DBT, New Delhi, India for financial
support (Grant No. BT/PR13997/Med/30/310/2010).
15. (a) Pal, M.; Subramanian, V.; Batchu, V. R.; Dager, I. Synlett 1965, 2004; (b)
Layek, M.; Lakshmi, U.; Kalita, D.; Barange, D. K.; Islam, A.; Mukkanti, K.; Pal, M.
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Rambabu, D.; Krishna, G. R.; Reddy, C. M.; Ravada, K.; Misra, P.; Iqbal, J.; Pal, M.
Med. Chem. Commun. 2011, 2, 1006; (b) Rao, R. M.; Reddy, U.; Nakhi, A.;
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Supplementary data
Supplementary data associated with this article can be found, in
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References and notes
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correlates the observed in vitro results of these molecules) this observation
however was specific for these molecules only and perhaps do not account the
general binding mode of N-tosyl or N-mesyl derivatives with hSIRT1 and the
observed trend of their in vitro inhibitions of yeast Sir 2.
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