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 by1 H 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.

Synthesis of dextran–phenoxodiol and evaluation of its physical stability and biological activity

Cirillo G.;
2019

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 by1 H 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.
Anti-angiogenic
Anti-tumor
Conjugate
Dextran
Phenoxodiol
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11770/305639
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