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.
The present study was carried out to evaluate anti-Helicobacter pylori and its associated urease activity of labdane diterpenoids isolated from Andrographis paniculata. A molecular docking analysis was performed by using ArgusLab 4.0.1 software. The results obtained indicate that compound A possesses strong inhibition to H. pylori, 28 ± 2.98 (minimum inhibitory concentration, 9 µg/mL), and its urease, 85.54 ± 2.62% (IC50 , 20.2 µg/mL). Compounds B, C, and D also showed moderate inhibition to H. pylori and its urease. The obtained results were in agreement with the molecular docking analysis of compounds. The phytochemicals under investigation were found to be promising antibacterial agents. Moreover, the isolated compounds can be considered as a resource for searching novel anti-H. pylori agents possessing urease inhibition.
Structural diversity of flavonoids and biological activities has remained an important discourse in the mainstream of flavonoid research. In the present studies different class of flavonoids such as flavones, flavanones and flavanolols were evaluated for their antiangiogenic, cytotoxic and antioxidant activities. The anti-angiogenic activity was evaluated using in vivo chorioallantoic membrane model (CAM), antioxidant potential and kinetics of free radical scavenging activity was determined using DPPH (2, 2-diphenyl-1-picryl hydrazine) and superoxide anion radical (SOR) scavenging assays, while cytotoxicity against selected cancer cell lines was carried out using MTT cell viability assay. The physicochemical properties/quantum chemical discriptors of the selected flavonoids were calculated using BioMed CAChe 6.1.10 drug. 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) and others from human origin. The results of the present investigation are discussed in the mainstream of structure activity relationship which may be useful in translating flavonoids as therapeutic molecules targeting angiogenesis.
References
1. Gacche R. N. Shegokar Harshala, Gond Dhananjay , A. D. Jadhav and Ghole Vikram. (2010). Effect of Hydroxyl Substitution of Flavone on Antiangiogenic and Free Radical Scavenging Activities: A Structure Activity Relationship Studies Using Computational Tools. European J. Pharmaceutical Science 39, 37-44.
2. Gacche R. N. Shegokar Harshala, Gond Dhananjay , Zhenzhou Yang, A. D. Jadhav (2011). Evaluation of selected flavonoids as antiangiogenic, anticancer and radical scavenging agents: an experimental and in silico analysis. Cell Biochemistry and Biophysics 61, 651-663. DOI 10.1007/s12013-011-9252-z.
3. Gacche RN and Meshram RJ (2013) Targeting Tumor Micro-environment for Design and Development of Novel Anti-angiogenic Agents Arresting Tumor Growth. Progress in Biophysics & Molecular Biology 113 (2013) 333-354.
Note: This abstract was not presented at the meeting.
Citation Format: Raju N. Gacche, Harshala D. Shegokar, Dhananjay S. Gond, Rohan J. Meshram. Structural peculiarities of flavonoids influence anti-angiogenic, cytotoxic and antioxidant effects: experimental and insilico analysis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1006. doi:10.1158/1538-7445.AM2014-1006
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