Cover Image

Evaluation of the interaction potential of synthetic ethylene glycol compounds with nuclear Factor ï«B

Srinivasan Narasimhan, Amin F. Majdalawieh, Imad A. Abu-Yousef, Dhivya Shanmugarajan, Vishvanathan Ramasubramanian


 In the last three decades, nuclear factor ï«B (NF-ï«B) has been the focus of many researchers who are interested in understanding the various molecular mechanisms involved in inflammatory diseases and cancer. Interference with NF-ï«B activity can cause many cellular abnormalities including tumorigenesis. In this study, we focus on examining the potential of ten synthetic ethylene glycol based compounds to interact with the binding site of NF-ï«B. Computational analysis reveals that the ethylene glycol compounds examined in this study display differential ability to interact with NF-ï«B. Parameters such as ALOGP, dock score, and internal energy were determined for each of the studied compounds. Seven compounds were found to interact with specific amino acid residues within the binding site of NF-ï«B. The specific amino acids involved in the interaction were mapped and the nature of interaction was identified. Since NF-ï«B is implicated in the development of many inflammatory and immune-related conditions including cancer, we predict that the ethylene glycol compounds examined in this study can be targeted for the development of therapeutic agents that can be employed in the prevention and/or treatment of various diseases including cancer.

Full Text:



P. P. Tak, G. S. Firestein, J. Clin. Invest., 2001, 107, 7-11.

Y. Yamamoto, R. B. Gaynor, J. Clin. Invest., 2001, 107, 135-142.

S. E. Shoelson, J. Lee, M. Yuan, Int. J. Obes. Relat. Metab. Disord., 2003, 27, S49-S52.

H. Clevers, Cell, 2004, 118, 671-674.

A. Kumar, Y. Takada, A. M. Boriek, B. B. Aggarwal, J. Mol. Med., 2004, 82, 434-448.

C. Monaco, E. Paleolog, Cardiovasc. Res., 2004, 61, 671-682.

A. F. Majdalawieh, H. S. Ro, Mediators Inflamm., 2010, 2010, 823821.

W. C. Sha, H. C. Liou, E. I. Tuomanen, D. Baltimore, Cell, 1995, 80, 321-330.

F. Weih, D. Carrasco, S. K. Durham, D. S. Barton, C. A. Rizzo, R. P. Ryseck, S. A. Lira, R. Bravo, Cell, 1995, 80, 331-340.

F. Kontgen, R. J. Grumont, A. Strasser, D. Metcalf, R. Li, D. Tarlinton, S. Gerondakis, Genes Dev., 1995, 9, 1965-1977.

J. H. Caamano, C. A. Rizzo, S. K. Durham, D. S. Barton, C. Raventos-Suarez, C. M. Snapper, R. Bravo, J. Exp. Med., 1998, 187, 185-196.

G. Franzoso, L. Carlson, L. Poljak, E. W. Shores, S. Epstein, A. Leonardi, A. Grinberg, T. Tran, T. Scharton-Kersten, M. Anver, P. Love, K. Brown, U. Siebenlist, J. Exp. Med., 1998, 187, 147-159.

P. A. Baeuerle, D. Baltimore, Genes Dev., 1989, 3, 1689-1698.

S. Ghosh, D. Baltimore, Nature, 1990, 344, 678-682.

M. J. May, S. Ghosh, Semin. Cancer Biol., 1997, 8, 63-73.

A. Israel, Trends Cell Biol., 2000, 10, 129-133.

M. S. Hayden, S. Ghosh, Genes Dev., 2004, 18, 2195-2224.

W. Wang, H. L. McLeod, J. Cassidy, Int. J. Cancer, 2003, 104, 504-511.

Y. Q. Li, Z. X. Zhang, Y. J. Xu, W. Ni, S. X. Chen, Z. Yang, D. Ma, Acta. Pharmacol. Sin., 2006, 27, 339-346.

R. Schreck, B. Meier, D. N. Mannel, W. Droge, P. A. Baeuerle, J. Exp. Med., 1992, 175, 1181-1194.

T. Aoki, H. Kataoka, R. Ishibashi, H. Nakagami, K. Nozaki, R. Morishita, N. Hashimoto, Neurosurgery, 2009, 64, 357-366.

S. Yamagishi, T. Matsui, K. Nakamura, H. Inoue, M. Takeuchi, S. Ueda, K. Fukami, S. Okuda, T. Imaizumi, Microvasc. Res., 2008, 75, 130-134.

J. Patocka, Z. Hon, Acta Medica, 2010, 53, 19-23.

R. Hess, M. J. Bartels, L. H. Pottenger, Arch Toxicol., 2004, 78, 671-680.

K. Gekko, T. Morikawa, J. Biochem., 1981, 90, 51-60.

D. Freifelder, Physical Biochemistry Applications to Biochemistry and Molecular Biology, 2nd ed., W.H. Freeman, New York, 1984.

R. H. Al-Shakhshir, F. E. Regnier, J. L. White, S. L. Hem, Vaccine, 1995, 13, 41-44.

S. L. Yowell, S. Blackwell, Cancer Treatment Rev., 2002, 28, S3-S6.

H. Wada, I. Imamura, M. Sako, S. Katagiri, S. Tarui, H. Nishimura, Y. Inada, Ann. NY Acad. Sci., 1990, 613, 95-108.

G. E. Francis, C. Delgado, D. Fisher, F. Malik, A. K. Agrawal, J. Drug Target., 1996, 3, 321-340.

C. L. van den Berg, G. N. Cox, C. A. Stroh, S. G. Hilsenbeck, C. N. Weng, M. J. McDermott, D. Pratt, C. K. Osborne, E. B. Coronado-Heinsohn, D. Yee, Eur. J. Cancer, 1997, 33, 1108-1113.

S. Narasimhan, S. Gopi, V. Ramasubramanian, D. P. Matharasi, S. Kannan, Indian Patent Application: 1951/CHE/2009.

H. M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, P. E. Bourne, Nucleic Acids Res., 2000, 28, 235-242.

H. M. Berman, Acta Crystallographica Section A: Foundations of Crystallography, 2008, A64, 88-95. 255.html

C. M. Venkatachalam, X. Jiang, T. Oldfield, M. Waldman, J. Mol. Graph. Model, 2003, 21, 289-307.

A. K. Ghose, G. M. Crippen, J. Comput. Chem., 1986, 7, 565-577.

A. K. Ghose, G. M. Crippen, J. Chem. Inf. Comput. Sci., 1987, 27, 21-35.

V. N. Viswanadhan, A. K. Ghose, G. R. Revankar, R. K. Robins, J. Chem. Inf. Comput. Sci., 1989, 29, 163-172.

A. K. Ghose, A. Pritchett, G. M. Crippen, J. Comput. Chem., 1988, 9, 80-90.

A. K. Ghose, V. N. Viswanadhan, J. J. Wendoloski, J. Phys. Chem. A., 1998, 102, 3762-3772.

C. A. Lipinski, F. Lombardo, B. W. Dominy, P. J. Feeney, Adv. Drug Del. Rev., 1997, 23, 3-25.

C. A. Lipinski, F. Lombardo, B.W. Dominy, P. J. Feeney, Adv. Drug Del. Rev., 2001, 46, 3-26.

T. I. Oprea, A. M. Davis, S. J. Teague, P. D. Leeson, J. Chem. Inf. Comput. Sci., 2001, 41, 1308-1315.



  • There are currently no refbacks.

Copyright (c) 2015 Mediterranean Journal of Chemistry