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Evaluation of Selected Flavonoids as Antiangiogenic, Anticancer, and Radical Scavenging Agents: An Experimental and In Silico Analysis

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Abstract

Developing antiangiogenic agents using natural products has remained a significant hope in the mainstream of anticancer research. In the present investigation series of flavonoids possessing di-, tri-, tetra-, and penta-hydroxy substitutions were evaluated as antiangiogenic agents using in vivo choriallantoic membrane model. The MTT-based cytotoxicity against selected cancer cell lines was carried out to determine the anticancer potential. The kinetics of free radical scavenging activities of these compounds was demonstrated using 2,2-diphenyl-1-picryl hydrazine (DPPH) and superoxide anion radicals (SORs). To understand the possible antiangiogenic mechanism, the selected flavonoids were docked in silico onto the proangiogenic peptides such as vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF-1α), and vascular endothelial growth factor receptor-2 (VEGFR2) from human origin. The results of the study shows that amongst the tested flavonoids, genistein (87.1%), kaempferol, (86.3%), and quercetin (84.7%) were found to be effective inhibitors of angiogenesis in CAM model. The antiangiogenic, cytotoxic, and antioxidant activities are discussed in light of structure–activity relationship using in silico approach and other drug-related properties were also calculated using BioMed CAChe V. 6.1.10. The results of the present study focus the isoflavone genistein, kaempferol, and quercetin as lead molecules for designing novel anti-tumor/antioxidant agents targeting angiogenesis.

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Acknowledgments

The authors are thankful to Council of Scientific & Industrial Research (CSIR), Human Resource Development Group, New Delhi for financial assistance (01(2249)/08/EMR-II), DSG thanks CSIR for SRF.

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Authors and Affiliations

  1. School of Life Sciences, Swami Ramanand Teerth Marathwada University, Nanded, 431 606, Maharashtra, India

    Rajesh N. Gacche, Harshala D. Shegokar, Dhananjay S. Gond, Zhenzhou Yang & Archana D. Jadhav

  2. Cancer Center, Daping Hospital and Surgery Research Institute, Third Military Medical University, Chongqing, 400042, China

    Zhenzhou Yang

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  1. Rajesh N. Gacche
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Correspondence to Rajesh N. Gacche.

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Gacche, R.N., Shegokar, H.D., Gond, D.S. et al. Evaluation of Selected Flavonoids as Antiangiogenic, Anticancer, and Radical Scavenging Agents: An Experimental and In Silico Analysis. Cell Biochem Biophys 61, 651–663 (2011). https://doi.org/10.1007/s12013-011-9251-z

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