Drug Design, Development and Therapy (Nov 2020)
In Ovo and In Silico Evaluation of the Anti-Angiogenic Potential of Syringin
Abstract
Charlaine A Aventurado,1 Junie B Billones,2 Ross D Vasquez,1,3,4 Agnes L Castillo1,3,4 1The Graduate School, University of Santo Tomas, Manila 1015, Philippines; 2Department of Physical Sciences and Mathematics, College of Arts and Sciences, University of the Philippines Manila, Manila, Philippines; 3Faculty of Pharmacy, University of Santo Tomas, Manila 1015, Philippines; 4Research Center for the Natural and Applied Sciences, University of Santo Tomas, Manila 1015, PhilippinesCorrespondence: Junie B BillonesDepartment of Physical Sciences and Mathematics, College of Arts and Sciences, University of the Philippines Manila, Padre Faura, Manila 1000, PhilippinesEmail [email protected]: Cancer is considered as one of the deadliest human diseases today. Angiogenesis, the propagation of new blood vessels from pre-existing vasculature, is a critical step in the progression of cancer as it is essential in the growth and metastasis of tumors. Hence, suppression of angiogenesis is a promising approach in cancer therapy. Syringin, a phenylpropanoid glycoside with a molecular formula of C17H24O9, has been found to exhibit chemopreventive effects. However, its anti-angiogenic activity and the underlying mechanism of action are still unknown.Methods: In this work, in ovo chorioallantoic membrane (CAM) assay has been conducted to evaluate the effect of syringin on neovascularization. Additionally, reverse molecular docking studies have been performed in order to identify the probable enzyme targets in the angiogenesis pathway.Results: Treatment with syringin showed significant dose-dependent inhibition of blood vessel length and junctions in the CAM of duck eggs; the anti-angiogenic activity of syringin at 100 μM and 200 μM is comparable with 200 μM of the positive control celecoxib. The results of reverse docking studies indicate that syringin binds the strongest to dihydrofolate reductase (DHFR) and, to some extent, with transforming growth factor-beta receptor type 1 (TGF-βR1), vascular endothelial growth factor receptor 2 (VEGFR2), and matrix metalloproteinase-2 (MMP-2). Furthermore, ADMET models revealed that syringin potentially possesses excellent pharmacokinetic and toxicity profiles.Conclusion: This study demonstrates the potential of syringin as an anti-angiogenic agent and elicits further investigations to establish its application in cancer suppression.Keywords: syringin, angiogenesis, cancer, molecular docking, reverse docking, dihydrofolate reductase, DHFR, TGF-ßR1, VEGFR2, MMP-2
