International E-publication: Publish Projects, Dissertation, Theses, Books, Souvenir, Conference Proceeding with ISBN.  International E-Bulletin: Information/News regarding: Academics and Research

Insilico Drug Designing of Potent Inhibitors for PDE7B, A Therapeutic Target for Leukemia

Author Affiliations

  • 1Department of Bioinformatics, U.C.S.T., Dehradun, UK, INDIA
  • 2 Department of Biotechnology, DDU Gorakhpur University, Gorakhpur, UP, INDIA

Res. J. of Pharmaceutical Sci., Volume 1, Issue (1), Pages 10-15, September,30 (2012)

Abstract

Leukemia is a cancer of the blood or bone marrow and is characterized by an abnormal proliferation of leukocytes. However, it affects more adults than children. In leukemia, the bone marrow makes abnormal white blood cells known as leukemia cells. They crowd out normal blood cells and made it hard for them to function properly. Leukemia is of two types, acute and chronic. According to the recent research, the PDE7B (Phosphodiesterase 7B) cAMP-specific Phosphodiesterase controls the levels of cAMP, promote apoptosis, and a process that is defective in chronic lymphocytic leukemia (CLL). Recent studies and research have found that lower cAMP levels contribute to the decreased apoptosis that causes CLL. The catalytic region lies between 172-410 residues and the active site residue lies at position of 173 – Histidine which acts as a proton donor. The ligand was developed using ChemSketch, which was docked with the receptor (target protein) and then ligand was allowed to grow with the help of LIGBUILDER in to a potential drug candidate, the drug has mild toxicity risks and having drug score of 0.34.It also have IC50 9.88e-003 and delta G 6.59 which is good enough to inhibit the expression of the protein PDE7B and effective in curing Leukemia.

References

  1. Aggarwal B.B. and Bhardwaj A., et al, Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies, Anticancer Res, 24(5A), 2783-840 (2004)
  2. Aggarwal B.B. and Kumar A., et al. Anticancer potential of curcumin: preclinical and clinical studies, Anticancer Res, 23(1A), 363-98 (2003)
  3. Aguayo A. and Kantarjian H., et al., Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes, Blood, 96(6), 2240-2245 (2000)
  4. Ahmed N. and Laverick L., et al. Ajoene, a garlic-derived natural compound, enhances chemotherapy-induced apoptosis in human myeloid leukaemia CD34-positive resistant cells, Anticancer Res, 21(5), 3519-23 (2001)
  5. Alter B.P., Cancer in Fanconi anemia, Cancer, 97(2), 425-40 (2003)
  6. Ames B.N., Cancer prevention and diet: help from single nucleotide polymorphisms, Proc Natl Acad Sci USA, 96(22), 12216-8 (1999)
  7. Ames B.N., Micronutrients prevent cancer and delay aging, Toxicol Lett, 102, 5-18 (1998)
  8. Ames B.N. and Shigenaga M.K., et al., Oxidants, antioxidants, and the degenerative diseases of aging, Proc Natl Acad Sci USA, 90(17), 7915-22 (1993)
  9. Anders O. and Nagel H.R., et al., Blood coagulation factors and proteinase inhibitors in cytostatic therapy of acute leukemia, Folia Haematol Int Mag Klin Morphol Blutforsch, 115(5), 769-80 (1988)
  10. Anderson G.D. and Rosito G., et al., Drug interaction potential of soy extract and Panax ginseng, J Clin Pharmacol, 43(6), 643-8 (2003)
  11. Arbiser J.L. and Klauber N., et al., Curcumin is an in vivo inhibitor of angiogenesis, Mol Med, 4(6), 376-83 (1998)
  12. Archer V.E., Association of nuclear fallout with leukemia in the United States, Arch Environ Health, 42(5), 263-71(1987)