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. 2015 Jul:577-578:35-48.
doi: 10.1016/j.abb.2015.04.009. Epub 2015 Apr 30.

Flavonoids as a scaffold for development of novel anti-angiogenic agents: An experimental and computational enquiry

R N Gacche  1 , R J Meshram  2 , H D Shegokar  2 , D S Gond  3 , S S Kamble  2 , V N Dhabadge  2 , B G Utage  4 , K K Patil  2 , R A More  2
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Flavonoids as a scaffold for development of novel anti-angiogenic agents: An experimental and computational enquiry

R N Gacche et al. Arch Biochem Biophys. 2015 Jul.

Abstract

Relationship between structural diversity and biological activities of flavonoids has remained an important discourse in the mainstream of flavonoid research. In the current study anti-angiogenic, cytotoxic, antioxidant and cyclooxygenase (COX) inhibitory activities of diverse class of flavonoids including hydroxyl and methoxy substituted flavones, flavonones and flavonols have been evaluated in the light of developing flavonoids as a potential scaffold for designing novel anti-antiangiogenic agents. We demonstrate anti-angiogenic potential of flavonoids using in vivo chorioallantoic membrane model (CAM) and further elaborate the possible structural reasoning behind observed anti-angiogenic effect using in silico methods. Additionally, we report antioxidant potential and kinetics of free radical scavenging activity using DPPH and SOR scavenging assays. Current study indicates that selected flavonoids possess considerable COX inhibition potential. Furthermore, we describe cytotoxicity of flavonoids against selected cancer cell lines using MTT cell viability assay. Structural analysis of in silico docking poses and predicted binding free energy values are not only in accordance with the experimental anti-angiogenic CAM values from this study but also are in agreement with the previously reported literature on crystallographic data concerning EGFR and VEGFR inhibition.

Keywords: Anti-angiogenesis; Antioxidant; Cyclooxygenase inhibition; Cytotoxicity; Flavonoids; Molecular docking; VEGFR and EGFR.

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