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Photopharmacology of Azo-Combretastatin-A4: Utilizing Tubulin Polymerization Inhibitors and Green Chemistry as the Key Steps

Author(s):

Shiva K. Rastogi*, Jennifer K Dunnigan, Adelyne C. Towne, Zhenze Zhao, Liqin Du and William J. Brittain   Pages 1 - 18 ( 18 )

Abstract:


Tubulin Polymerization Inhibitors (TPIs) are promising ligands utilized in chemotherapy for modern cancer treatment. However, the current TPIs exhibit many serious side effects that may pose limitations in chemotherapy. Combretastatin A-4 (CA-4) is a natural TPI that binds at the colchicine binding site located on microtubules. The only cis isomer of CA-4 is bio-active; however, due to its short half-life, it isomerizes quickly to its bio-inactive trans geometric isomer. For preventing shortcomings of CA-4, azobenzene based CA-4, called azo-CA-4 (azo-CA-4) is identified as a novel TPI. The geometric isomerization of azo- CA-4 can be controlled upon exposure to ultraviolet (UV) light to remotely control its bioactivity. Cis-azo-CA-4 is 200-500 times more active (IC50 = 0.2-10 μM) than trans-azo-CA-4 (IC50 = 50-110 μM) against various cancer cell lines. Photo-pharmacology uses light to control drug activity, introducing a unique mechanism to develop novel photo-responsive TPIs. Further, the green chemistry approach using ethanol and water as a green solvent in the synthesis of azo-CA-4 delivers advanced methodology in novel TPI development.

Keywords:

Photopharmacology, azo-combretastatin, tubulin, inhibitors, green chemistry, solvent.

Affiliation:

STEM LLC Capstone, Texas State University, Department of Chemistry and Biochemistry, Texas State University, 601 University Drive, San Marcos, TX-78666, STEM LLC Capstone, Texas State University, Department of Chemistry and Biochemistry, Texas State University, 601 University Drive, San Marcos, TX-78666, STEM LLC Capstone, Texas State University, Department of Chemistry and Biochemistry, Texas State University, 601 University Drive, San Marcos, TX-78666, STEM LLC Capstone, Texas State University, Department of Chemistry and Biochemistry, Texas State University, 601 University Drive, San Marcos, TX-78666, STEM LLC Capstone, Texas State University, Department of Chemistry and Biochemistry, Texas State University, 601 University Drive, San Marcos, TX-78666, STEM LLC Capstone, Texas State University, Department of Chemistry and Biochemistry, Texas State University, 601 University Drive, San Marcos, TX-78666



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