Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014, Article ID 979606, 12 pages
http://dx.doi.org/10.1155/2014/979606
Research Article

Development of Dual Inhibitors against Alzheimer’s Disease Using Fragment-Based QSAR and Molecular Docking

1Apaji Institute of Mathematics & Applied Computer Technology, Banasthali University, Tonk, Rajasthan 304022, India
2School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India
3Department of Biochemistry, University of Kashmir, Srinagar 190006, India

Received 17 December 2013; Revised 27 March 2014; Accepted 27 March 2014; Published 12 June 2014

Academic Editor: Jason E. Mcdermott

Copyright © 2014 Manisha Goyal et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. G. Benzi and A. Moretti, “Is there a rationale for the use of acetylcholinesterase inhibitors in the therapy of Alzheimer's disease?” European Journal of Pharmacology, vol. 346, no. 1, pp. 1–13, 1998. View at Publisher · View at Google Scholar · View at Scopus
  2. F. Belluti, M. Bartolini, G. Bottegoni et al., “Benzophenone-based derivatives: a novel series of potent and selective dual inhibitors of acetylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation,” European Journal of Medicinal Chemistry, vol. 46, no. 5, pp. 1682–1693, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. D. M. Walsh and D. J. Selkoe, “Deciphering the molecular basis of memory failure in Alzheimer's disease,” Neuron, vol. 44, no. 1, pp. 181–193, 2004. View at Publisher · View at Google Scholar · View at Scopus
  4. S.-J. Choi, J.-H. Cho, I. Im et al., “Design and synthesis of 1,4-dihydropyridine derivatives as BACE-1 inhibitors,” European Journal of Medicinal Chemistry, vol. 45, no. 6, pp. 2578–2590, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. H.-W. Klafki, M. Staufenbiel, J. Kornhuber, and J. Wiltfang, “Therapeutic approaches to Alzheimer's disease,” Brain, vol. 129, no. 11, pp. 2840–2855, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. P. D. Edwards, J. S. Albert, M. Sylvester et al., “Application of fragment-based lead generation to the discovery of novel, cyclic amidine β-secretase inhibitors with nanomolar potency, cellular activity, and high ligand efficiency,” Journal of Medicinal Chemistry, vol. 50, no. 24, pp. 5912–5925, 2007. View at Publisher · View at Google Scholar · View at Scopus
  7. A. Aguzzi and T. O'Connor, “Protein aggregation diseases: pathogenicity and therapeutic perspectives,” Nature Reviews Drug Discovery, vol. 9, no. 3, pp. 237–248, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. C. A. Kelly, R. J. Harvey, and H. Cayton, “Drug treatments for Alzheimer's disease,” British Medical Journal, vol. 314, no. 7082, pp. 693–694, 1997. View at Google Scholar
  9. P. J. Whitehouse, “Cholinergic therapy in dementia,” Acta Neurologica Scandinavica, Supplement, vol. 88, no. 149, pp. 42–45, 1993. View at Google Scholar · View at Scopus
  10. L. J. Scott and K. L. Goa, “Galantamine: a review of its use in Alzheimer's disease,” Drugs, vol. 60, no. 5, pp. 1095–1122, 2000. View at Google Scholar · View at Scopus
  11. A. Yan and K. Wang, “Quantitative structure and bioactivity relationship study on human acetylcholinesterase inhibitors,” Bioorganic & Medicinal Chemistry Letters, vol. 22, no. 9, pp. 3336–3342, 2012. View at Publisher · View at Google Scholar
  12. J. Birks, “Cholinesterase inhibitors for Alzheimer's disease,” Cochrane Database of Systematic Reviews, no. 1, Article ID CD005593, 2006. View at Google Scholar · View at Scopus
  13. S. A. Areosa, F. Sherriff, and R. McShane, “Memantine for dementia,” Cochrane Database of Systematic Reviews, no. 2, Article ID CD003154, 2006. View at Google Scholar · View at Scopus
  14. M. W. Weiner, C. Sadowsky, J. Saxton et al., “Magnetic resonance imaging and neuropsychological results from a trial of memantine in Alzheimer's disease,” Alzheimer's and Dementia, vol. 7, no. 4, pp. 425–435, 2011. View at Publisher · View at Google Scholar · View at Scopus
  15. D. J. Selkoe, “Translating cell biology into therapeutic advances in Alzheimer's disease,” Nature, vol. 399, supplement, pp. A23–A31, 1999. View at Google Scholar · View at Scopus
  16. T. Guo and D. W. Hobbs, “Development of BACE1 inhibitors for Alzheimer's disease,” Current Medicinal Chemistry, vol. 13, no. 15, pp. 1811–1829, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. L. Piazzi, A. Cavalli, F. Colizzi et al., “Multi-target-directed coumarin derivatives: hAChE and BACE1 inhibitors as potential anti-Alzheimer compounds,” Bioorganic & Medicinal Chemistry Letters, vol. 18, no. 1, pp. 423–426, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. A. Cavalli, M. L. Bolognesi, A. Mìnarini et al., “Multi-target-directed ligands to combat neurodegenerative diseases,” Journal of Medicinal Chemistry, vol. 51, no. 3, pp. 347–372, 2008. View at Publisher · View at Google Scholar · View at Scopus
  19. L. Piazzi, A. Rampa, A. Bisi et al., “3-(4-{[benzyl(methyl)amino]methyl}-phenyl)-6,7-dimethoxy-2H-2-chromenone (AP2238) inhibits both acetylcholinesterase and acetylcholinesterase-induced β-amyloid aggregation: a dual function lead for Alzheimer's disease therapy,” Journal of Medicinal Chemistry, vol. 46, no. 12, pp. 2279–2282, 2003. View at Publisher · View at Google Scholar · View at Scopus
  20. S. L. Cole and R. Vassar, “BACE1 structure and function in health and Alzheimer's disease,” Current Alzheimer Research, vol. 5, no. 2, pp. 100–120, 2008. View at Publisher · View at Google Scholar · View at Scopus
  21. R. E. Tanzi and L. Bertram, “Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective,” Cell, vol. 120, no. 4, pp. 545–555, 2005. View at Publisher · View at Google Scholar · View at Scopus
  22. L. Zou, R. Yang, P. Zhang, and Y. Dai, “The enhancement of amyloid precursor protein and β-site amyloid cleavage enzyme 1 interaction: amyloid-β production with aging,” International Journal of Molecular Medicine, vol. 25, no. 3, pp. 401–407, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. R. Sheng, X. Lin, J. Zhang et al., “Design, synthesis and evaluation of flavonoid derivatives as potent AChE inhibitors,” Bioorganic & Medicinal Chemistry, vol. 17, no. 18, pp. 6692–6698, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. G. Bottegoni, A. D. Favia, M. Recanatini, and A. Cavalli, “The role of fragment-based and computational methods in polypharmacology,” Drug Discovery Today, vol. 17, no. 1-2, pp. 23–34, 2012. View at Publisher · View at Google Scholar · View at Scopus
  25. C. B. Breitenlechner, T. Wegge, L. Berillon et al., “Structure-based optimization of novel azepane derivatives as PKB inhibitors,” Journal of Medicinal Chemistry, vol. 47, no. 6, pp. 1375–1390, 2004. View at Publisher · View at Google Scholar · View at Scopus
  26. Y. Luo, A. R. Shoemaker, X. Liu et al., “Potent and selective inhibitors of Akt kinases slow the progress of tumors in vivo,” Molecular Cancer Therapeutics, vol. 4, no. 6, pp. 977–986, 2005. View at Publisher · View at Google Scholar · View at Scopus
  27. S. K. Deshpande, “Molecule fragmentation scheme and method for designing new molecules,” in Google Patents, 2008. View at Google Scholar
  28. J. Verma, V. M. Khedkar, and E. C. Coutinho, “3D-QSAR in drug design—a review,” Current Topics in Medicinal Chemistry, vol. 10, no. 1, pp. 95–115, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. VLifeMDS: Molecular Design Suite, Vlife Sciences Technologies Pvt. Ltd., Pune, India, 3rd edition, 2004.
  30. K. Baumann, “An alignment-independent versatile structure descriptor for QSAR and QSPR based on the distribution of molecular features,” Journal of Chemical Information and Computer Sciences, vol. 42, no. 1, pp. 26–35, 2002. View at Publisher · View at Google Scholar · View at Scopus
  31. S. Ajmani and S. A. Kulkarni, “Application of GQSAR for scaffold hopping and lead optimization in multitarget inhibitors,” Molecular Informatics, vol. 31, no. 6-7, pp. 473–490, 2012. View at Google Scholar
  32. R. D. Cramer III, D. E. Patterson, and J. D. Bunce, “Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins,” Journal of the American Chemical Society, vol. 110, no. 18, pp. 5959–5967, 1988. View at Google Scholar · View at Scopus
  33. A. Afantitis, G. Melagraki, H. Sarimveis, O. Igglessi-Markopoulou, and G. Kollias, “A novel QSAR model for predicting the inhibition of CXCR3 receptor by 4-N-aryl-[1,4] diazepane ureas,” European Journal of Medicinal Chemistry, vol. 44, no. 2, pp. 877–884, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. A. Golbraikh and A. Tropsha, “Beware of q2!,” Journal of Molecular Graphics and Modelling, vol. 20, no. 4, pp. 269–276, 2002. View at Publisher · View at Google Scholar · View at Scopus
  35. www.rcsb.org/pdb.
  36. Schrodinger, “Schrodinger suite,” LLC, New York, NY, USA, 2009.
  37. A. C. Wallace, R. A. Laskowski, and J. M. Thornton, “LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions,” Protein Engineering, vol. 8, no. 2, pp. 127–134, 1995. View at Google Scholar · View at Scopus
  38. A. Nayyar, V. Monga, A. Malde, E. Coutinho, and R. Jain, “Synthesis, anti-tuberculosis activity, and 3D-QSAR study of 4-(adamantan-1-yl)-2-substituted quinolines,” Bioorganic and Medicinal Chemistry, vol. 15, no. 2, pp. 626–640, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. D. Pal, C. Sengupta, and A. De, “A new topochemical descriptor (TAU) in molecular connectivity concept: part I—aliphatic compounds,” Indian Journal of Chemistry B, vol. 27, pp. 734–739, 1988. View at Google Scholar
  40. D. K. Pal, C. Sengupta, and A. U. De, “Introduction of a novel topochemical index and exploitation of group connectivity concept to achieve predictability in QSAR and RDD,” Indian Journal of Chemistry B, vol. 28, no. 3, pp. 261–267, 1989. View at Google Scholar · View at Scopus
  41. K. Roy and R. N. Das, “On some novel extended topochemical atom (ETA) parameters for effective encoding of chemical information and modelling of fundamental physicochemical properties,” SAR and QSAR in Environmental Research, vol. 22, no. 5-6, pp. 451–472, 2011. View at Publisher · View at Google Scholar · View at Scopus
  42. K. Roy and G. Ghosh, “Exploring QSARs with Extended Topochemical Atom (ETA) indices for modeling chemical and drug toxicity,” Current Pharmaceutical Design, vol. 16, no. 24, pp. 2625–2639, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. L. H. Hall and L. B. Kier, “The molecular connectivity chi indexes and kappa shape indexes in structure-property modeling,” Reviews in Computational Chemistry, vol. 2, pp. 367–422, 1991. View at Publisher · View at Google Scholar