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Maged Henary

Assistant Professor
Education

Georgia State University, Ph.D. (1997-2000)
Georgia Institute of Technology, Postdoctoral Research Fellow (2001-2004)
Visiting Lecturer, Georgia State University (2005-2006)
Lecturer, Georgia State University (2007-2010)
Assistant Professor, Georgia State University (2011-present)

Biography

Research in the Henary Laboratory focuses on synthetic organic chemistry. Our group is interested in the design, synthesis and development of pharmaceutical agents, other chemical entities suitable for therapeutic use and imaging technology, such as cancer imaging dyes, invisible markers, and fluorescent probes. We aim to establish several collaborations with analytical chemists, biologists, biochemists, and physicians to facilitate the design and developmental process of small molecules with significant biological activity.

Synthesis of Endocrine Specific Near-Infrared Fluorophores (ESNFs)-

Through collaboration with the Center of Molecular Imaging at Harvard Medical School, specifically the Choi and Frangioni Laboratories, we are working to design, synthesize and analyze NIR fluorophores that successfully image endocrine glands for intraoperative use.

Identification of normal endocrine glands and their tumors are of critical importance to preserve normal tissue, and to remove diseased tissue, respectively.

There are no contrast agents available to highlight normal tissue, such as the thyroid gland, which needs to be avoided for example, during head and neck surgery.

Through extensively modifying the pentacyanine structure (utilizing Log(P) values) we have developed several ESNFs for image-guided surgery of various glands.

Synthesis of Tri- and Pentamethine  Cyanine Dyes for Selectively Binding G-Quadruplex DNA

droppedImage_6(d1)Telomerase is overactive in cancer cells and provides endless replication processes to the mutated cells. Inhibition of telomerase has been recognized as a viable strategy to prevent growth of tumors. This chemotherapeutic strategy to specifically target G-quadruplex DNA in cancer cells with no apparent side effects is being heavily investigated. To date, no small molecules have been reported that satisfy the conditions needed for medicinal use.

BRACO-19 was identified as the lead compound in this field and was removed from clinical trials due to cytotoxicity from Duplex DNA binding. Our data strongly suggest a) an increase in G-quadruplex binding with certain carbocyanine dyes, b) active compounds have a net positive charge, c) strong binding properties to G-quadruplex structures while sparing duplex DNA.

This suggests the potential usefulness of these carbocyanine compounds as novel anti-cancer agents. Our goal is to design and synthesize additional condensed and positively charged tri- and pentacarbocyanine dyes as G-quadruplex targeting compounds for use as anti-cancer therapeutic agents.

Quadruplex Image Side 2MBJ(d2)Quadruplex Image Top 2MBJ(d3)

Publications

Representative Publications:

  1. Yadav, Y., Owens, E.A., Sharma, V., Aneja, R. Synthesis and evaluation of antiproliferative activity of a novel series of hydroxychavicol analogs 2014 75 1-10.
  2. Mapp, C. T., Owens, E. A., Henary, M. M., Grant, K. B., Oxidative cleavage of DNA by pentamethine carbocyanine dyes irradiated with long-wavelength visible light. Bioorganic & Medicinal Chemistry Letters, Available online 25 November 2013.
  3.  Nanjunda, R., Owens, E. A., Mickelson, L., Dost, T. L., Stroeva, E. M. E, Huynh, H. T., Germann, M. W., Henary, M. M., Wilson, W. D., Selective G-Quadruplex DNA Recognition by a New Class of Designed Cyanines Molecules 2013, 18(11), 13588-13607.
  4.  A. Levitz, M. Henary, Synthesis and applications of unsymmetrical carbocyanine dyes, Dyes and Pigments, 2013, 99, 3, 1107-1116.
  5.  Choi, H. S., Gibbs, S. L., Lee, J., H., Kim, S. H., Ashitate, Y., Liu, F., Hyun, H., Park G. L., Xie, Y., Bae, S., Henary, M., Frangioni, J. V. “Targeted Zwitterionic Near-Infrared Fluorophores for Improved Optical Imaging”. Nature Biotechnol2013, In Press