Display options
Cite
AbdelHafez EM, Diamanduros A, Negureanu L, et al. Computational and synthetic studies towards improving rescinnamine as an inducer of MSH2-dependent apoptosis in cancer treatment. Mol Cancer Biol. 2013;1(1)
AbdelHafez, E. M., Diamanduros, A., Negureanu, L., Luy, Y., Bean, J. H., Zielke, K., Crowe, B., Vasilyeva, A., Clodfelter, J. E., Aly, O. M., Abuo-Rahma, G. E., Scarpinato, K. D., Salsbury, F. R., & King, S. B. (2013). Computational and synthetic studies towards improving rescinnamine as an inducer of MSH2-dependent apoptosis in cancer treatment. Molecular cancer biology, 1(1), .
AbdelHafez, ElShimaa M N, et al. "Computational and synthetic studies towards improving rescinnamine as an inducer of MSH2-dependent apoptosis in cancer treatment." Molecular cancer biology vol. 1,1 (2013).
AbdelHafez EM, Diamanduros A, Negureanu L, Luy Y, Bean JH, Zielke K, Crowe B, Vasilyeva A, Clodfelter JE, Aly OM, Abuo-Rahma GE, Scarpinato KD, Salsbury FR, King SB. Computational and synthetic studies towards improving rescinnamine as an inducer of MSH2-dependent apoptosis in cancer treatment. Mol Cancer Biol. 2013;1(1). PMID: 25485184; PMCID: PMC4254817.
Copy Download .nbib Format: NLM
Share it on

Mol Cancer Biol. 2013;1(1).

Computational and synthetic studies towards improving rescinnamine as an inducer of MSH2-dependent apoptosis in cancer treatment.

Molecular cancer biology

ElShimaa M N AbdelHafez, Andrew Diamanduros, Lacramioara Negureanu, Yan Luy, J Hayley Bean, Katherine Zielke, Brittany Crowe, Aksana Vasilyeva, Jill E Clodfelter, Omar M Aly, Gamal El-Din A A Abuo-Rahma, Karin D Scarpinato, Freddie R Salsbury, S Bruce King

Affiliations

  1. Department of Chemistry, Wake Forest University, Winston-Salem, NC.
  2. Department of Biology, Georgia Southern University, Statesboro, GA.
  3. Department of Physics, Wake Forest University, Winston-Salem, NC.
  4. Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC; now: St. Jude Hospital, Memphis, TN.
  5. Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC.
  6. Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia , Egypt.

PMID: 25485184 PMCID: PMC4254817

Abstract

We, and others, have previously shown that mismatch repair proteins, in addition to their repair function, contribute to cell death initiation. In response to some drugs, this cell death activity is independent of the repair function of the proteins. Rescinnamine, a derivative of the indole alkaloid reserpine, a drug used to treat hypertension several decades ago, was shown to target the cell death-initiating activity of mismatch repair proteins. When used in animals, the hypotensive action of this drug prevents applying appropriate concentrations for statistically significant tumor reduction. Using a combination of computational modeling, chemical synthesis and cell assays, we determine how rescinnamine can be structurally modified and what effect these modifications have on cell survival. These results inform further computational modeling to suggest new synthetic lead molecules to move toward further biological testing.

References

  1. J Biomol Struct Dyn. 2012;29(4):757-76 - PubMed
  2. Br Med J. 1960 Dec 24;2(5216):1848-50 - PubMed
  3. Nucleic Acids Res. 2006 Apr 28;34(8):2173-85 - PubMed
  4. J Nucleic Acids. 2010 Sep 13;2010:null - PubMed
  5. J Comput Chem. 2009 Dec;30(16):2785-91 - PubMed
  6. Cancer Res. 1997 Sep 15;57(18):3949-55 - PubMed
  7. DNA Repair (Amst). 2009 Jan 1;8(1):103-13 - PubMed
  8. Mutat Res. 2006 Mar;612(2):115-49 - PubMed
  9. J Biol Chem. 2009 May 22;284(21):14029-39 - PubMed
  10. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5128-32 - PubMed
  11. Curr Opin Pharmacol. 2010 Dec;10(6):738-44 - PubMed
  12. Chem Commun (Camb). 2009 May 7;(17):2281-3 - PubMed

Publication Types

Grant support