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

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

Volume: 25 Issue: 20

Author(s): Shiva K. Rastogi*, Jennifer K. Dunnigan, Adelyne C. Towne, Zhenze Zhao, Liqin Du and William J. Brittain

Affiliation:

• Department of Chemistry and Biochemistry, Texas State University, 601 University Drive, San Marcos, TX-78666,United States

Keywords: Photopharmacology, azo-combretastatin, tubulin, inhibitors, green chemistry, solvent, TPI.

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.

Cite this article as:

Rastogi K. Shiva *, Dunnigan K. Jennifer , Towne C. Adelyne , Zhao Zhenze, Du Liqin and Brittain J. William , Photopharmacology of Azo-Combretastatin-A4: Utilizing Tubulin Polymerization Inhibitors and Green Chemistry as the Key Steps, Current Organic Chemistry 2021; 25 (20) . https://dx.doi.org/10.2174/1385272825666210526151222