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Paper
transportation at the specic site in the body to reactivate 10 S. B. Bharate, L. Guo, T. E. Reeves, D. M. Cerasoli and
inhibited AChE.
C. M. Thompson, Bioorg. Med. Chem. Lett., 2009, 19, 5101–
5104.
11 K. Musilek, O. Holas, D. Jun, V. Dohnal, F. G. Moore,
V. Opletalova, M. Dolezala and K. Kuca, Bioorg. Med.
Chem., 2007, 15, 6733–6741.
12 K. Kuca, J. Bielavsky, J. Cabal and M. Bielavska, Tetrahedron
Lett., 2003, 44, 3123–3125.
13 F. Ekstrom, J. C. Astot and Y. P. Pang, Clin. Pharmacol. Ther.,
2007, 82, 282–293.
14 A. Luettringhaus and I. Hagedorn, Drug Res., 1964, 14, 1–5.
15 J. Acharya, D. K. Dubey, A. K. Srivastava and S. K. Raza,
Toxicol. In Vitro, 2011, 25, 251–256.
16 J. J. Kassa, J. Toxicol., Clin. Toxicol., 2002, 40, 803–816.
17 F. Worek, G. Reiter, P. Eyer and L. Szinicz, Arch. Toxicol.,
2002, 76, 523–529.
18 J. G. Clement and N. Erhardt, Arch. Toxicol., 1994, 68, 648–
659.
4. Conclusion
In this study mono-quaternary oximes were synthesized as
reactivator for paraoxon inhibited eelAChE by variation in the
carbon chain attached with the –N position of 4-pyridoxime
moiety. These oximes were studied for their binding affinity
with eelAChE. Further, this binding was validated with the
molecular modeling studies on the basis of Glide Gscore, p–p
interaction and hydrophobic interaction on the active site of
AChE. These synthesized oximes were found to be effective
reactivators towards the paraoxon inhibited eelAChE as
compared to the known reactivator 2-PAM. 4PBB and 4PBP have
high reactivation potency as compared to 4PCB. Furthermore,
they also showed drug likeliness behavior by showing effective
pharmacokinetics properties with human serum albumin.
19 W. K. Berry, Biochem. Pharmacol., 1971, 20, 1333–1334.
20 X. Q. Feng, Z. S. Zeng, Y. H. Liang, F. E. Chen,
C. Pannecouque, J. Balzarini and E. D. Clercq, Bioorg. Med.
Chem., 2010, 18, 2370–2374.
21 S. R. Chennamaneni, V. Vobalaboina and A. Garlapati,
Bioorg. Med. Chem. Lett., 2005, 15, 3076–3080.
22 A. K. Sikder, A. K. Ghosh and D. K. Jaiswal, J. Pharm. Sci.,
1993, 82, 258–261.
Acknowledgements
We thank Dr R. P. Tripathi, Director, INMAS, DRDO for
providing the necessary facilities and CSIR for nancial assis-
tance to the rst and second authors during the course of the
research work.
23 F. Ekstrom, A. Hornberg, E. Artursson, L. G. Hammarstrom,
G. Schneider and Y. P. Pang, PLoS One, 2009, 4(6), e5957.
24 E. Artursson, P. O. Andersson, C. Akfur, A. Linusson,
S. Borjegren and F. Ekstrom, Biochem. Pharmacol., 2013,
85, 1389–1397.
25 R. A. Friesner, R. B. Murphy, M. P. Repasky, L. L. Frye,
J. R. Greenwood, T. A. Halgren, P. C. Sanschagrin and
D. T. Mainz, J. Med. Chem., 2006, 49, 6177–6196.
26 K. Musilek, M. KomLoova, O. Holas, A. Horova, M. Pohanka,
F. G. Moore, V. Dohnal, M. Dolezal and K. Kuca, Bioorg. Med.
Chem., 2011, 19, 754–762.
Notes and references
1 M. C. De Koning, M. J. A. Joosen, D. Noort, A. Van Zuylen and
M. C. Tromp, Bioorg. Med. Chem., 2011, 19, 588–594.
2 Z. Kovarik, N. Macek, R. K. Sit, Z. Radic, V. V. Fokin,
K. B. Sharpless and P. Taylor, Chem.–Biol. Interact., 2013,
203, 77–80.
3 T. H. Kim, K. Kuca, D. Jun and Y. S. Jung, Bioorg. Med. Chem.
Lett., 2005, 15, 2914–2917.
4 K. Musilek, K. Kuca, D. Jun, V. Dohnal and M. Dolezal,
Bioorg. Med. Chem. Lett., 2006, 16, 622–627.
5 K. Musilek, O. Holas, K. Kuca, D. Jun, V. Dohnal and
M. Dolezal, Bioorg. Med. Chem. Lett., 2006, 16, 5673–5676.
6 K. Musilek, J. Roder, M. KomLoova, O. Holas, M. Hbinova,
M. Pohanka, V. Dohnal, V. Opletalova, K. Kuca and
Y. S. Jung, Bioorg. Med. Chem. Lett., 2011, 21, 150–154.
7 S. B. Bharate, L. Guo, T. E. Reeves, D. M. Cerasoli and
C. M. Thompson, Bioorg. Med. Chem., 2010, 18, 787–794.
8 J. Acharya, A. K. Gupta, A. Mazumder and D. K. Dubey,
Toxicol. In Vitro, 2008, 22, 525–530.
27 G. L. Ellman, D. K. Courtney, V. Andreas and
R. M. Featherstone, Biochem. Pharmacol., 1961, 7, 88–95.
28 H. H. Sun, J. Zhang, Y. Z. Zhang, L. Y. Yang, L. L. Yuan and
Y. Liu, Mol. Biol. Rep., 2012, 39, 5115–5123.
29 P. Bourassa, S. Dubeau, G. M. Maharvi, A. H. Fauq,
T. J. Thomas and H. A. T. Riahi, Biochimie, 2011, 93, 1089–
1101.
30 H. X. Zhang and P. Mei, J. Solution Chem., 2009, 38, 351–355.
31 N. Chadha, A. K. Tiwari, V. Kumar, S. Lal, M. D. Milton and
A. K. Mishra, J. Biomol. Struct. Dyn., 2014, 29, 1–13.
9 G. Sinko, J. Brglez and Z. Kovarik, Chem.–Biol. Interact., 2010,
187, 172–176.
23480 | RSC Adv., 2015, 5, 23471–23480
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