AUTHOR=Yee Eugene M. H. , Cirillo Giuseppe , Brandl Miriam B. , Black David StC , Vittorio Orazio , Kumar Naresh TITLE=Synthesis of Dextran–Phenoxodiol and Evaluation of Its Physical Stability and Biological Activity JOURNAL=Frontiers in Bioengineering and Biotechnology VOLUME=7 YEAR=2019 URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2019.00183 DOI=10.3389/fbioe.2019.00183 ISSN=2296-4185 ABSTRACT=

Phenoxodiol, an isoflavene anti-tumor agent, was conjugated on the polysaccharide dextran using immobilized laccase as biocatalyst. The success of the enzymatic conjugation was determined by UV-vis spectrophotometry and its functionalization degree was assessed by 1H NMR and was found to be 3.25 mg phenoxodiol/g of conjugate. An accelerated stability test showed that the resultant conjugate was nine times more stable than the free phenoxodiol when tested for its residual anti-oxidant activity with the Folin–Ciocalteu assay. The in vitro anti-proliferative activity of the conjugate was evaluated against neuroblastoma SKN-BE(2)C, triple-negative breast cancer MDA-MB-231, and glioblastoma U87 cancer cells. The conjugate was shown to be generally more potent than phenoxodiol against all three cell types tested. Additionally, the cytotoxicity and anti-angiogenic activity of the conjugate were also evaluated against non-malignant human lung fibroblast MRC-5 and human microvascular endothelial cells HMEC-1, respectively. The conjugate was found to be 1.5 times less toxic than phenoxodiol while mostly retaining 62% of its anti-angiogenic activity in the conjugate form. This study provides further evidence that the conjugation of natural product-derived drugs onto polysaccharide molecules such as dextran can lead to better stability and enhanced biological activity of the conjugate compared to the free drug alone.