Saha Sanjib, Islam Md Khirul, Shilpi Jamil A, Hasan Shihab
Pharmacy Discipline, Life Science School, Khulna University, Khulna, 9208 Bangladesh.
Pharmacy Discipline, Life Science School, Khulna University, Khulna, 9208 Bangladesh ; Centre for Natural Products and Drug (CENAR), University of Malaya, 50603 Kuala Lumpur, Malaysia.
In Silico Pharmacol. 2013 Jul 29;1:11. doi: 10.1186/2193-9616-1-11. eCollection 2013.
Angiogenesis, or new blood vessel formation from existing one, plays both beneficial and detrimental roles in living organisms in different aspects. Vascular endothelial growth factor (VEGF), a signal protein, well established as key regulator of vasculogenesis and angiogenesis. VEGF ensures oxygen supply to the tissues when blood supply is not adequate, or tissue environment is in hypoxic condition. Limited expression of VEGF is necessary, but if it is over expressed, then it can lead to serious disease like cancer. Cancers that have ability to express VEGF are more efficient to grow and metastasize because solid cancers cannot grow larger than a limited size without adequate blood and oxygen supply. Anti-VEGF drugs are already available in the market to control angiogenesis, but they are often associated with severe side-effects like fetal bleeding and proteinuria in the large number of patients. To avoid such side-effects, new insight is required to find potential compounds as anti-VEGF from natural sources. In the present investigation, molecular docking studies were carried out to find the potentiality of Withaferin A, a key metabolite of Withania somnifera, as an inhibitor of VEGF.
Molecular Docking studies were performed in DockingServer and SwissDock. Bevacizumab, a commercial anti-VEGF drug, was used as reference to compare the activity of Withaferin A. X-ray crystallographic structure of VEGF, was retrieved from Protein Data Bank (PDB), and used as drug target protein. Structure of Withaferin A and Bevacizumab was obtained from PubChem and ZINC databases. Molecular visualization was performed using UCSF Chimera.
Withaferin A showed favorable binding with VEGF with low binding energy in comparison to Bevacizumab. Molecular Docking studies also revealed potential protein-ligand interactions for both Withaferin A and Bevacizumab.
Conclusively our results strongly suggest that Withaferin A is a potent anti-VEGF agent as ascertained by its potential interaction with VEGF. This scientific hypothesis might provide a better insight to control angiogenesis as well as to control solid cancer growth and metastasis.
血管生成，即从现有血管形成新的血管，在生物体的不同方面发挥着有益和有害的作用。血管内皮生长因子（VEGF）是一种信号蛋白，已被公认为血管生成和血管生成的关键调节因子。当血液供应不足或组织环境处于缺氧状态时，VEGF可确保向组织提供氧气。VEGF的有限表达是必要的，但如果过度表达，则可能导致癌症等严重疾病。能够表达VEGF的癌症在生长和转移方面更有效，因为实体癌在没有足够的血液和氧气供应的情况下无法生长到超过有限的大小。市场上已经有抗VEGF药物来控制血管生成，但它们通常与大量患者的严重副作用相关，如胎儿出血和蛋白尿。为了避免此类副作用，需要新的见解来从天然来源寻找潜在的抗VEGF化合物。在本研究中，进行了分子对接研究，以确定印度人参的关键代谢产物Withaferin A作为VEGF抑制剂的潜力。
在DockingServer和SwissDock中进行分子对接研究。使用商业抗VEGF药物贝伐单抗作为参考来比较Withaferin A的活性。从蛋白质数据库（PDB）中检索VEGF的X射线晶体结构，并将其用作药物靶蛋白。Withaferin A和贝伐单抗的结构从PubChem和ZINC数据库中获得。使用UCSF Chimera进行分子可视化。
与贝伐单抗相比，Withaferin A与VEGF显示出良好的结合，结合能较低。分子对接研究还揭示了Withaferin A和贝伐单抗潜在的蛋白质-配体相互作用。
我们的结果有力地表明，Withaferin A通过其与VEGF的潜在相互作用被确定为一种有效的抗VEGF剂。这一科学假设可能为控制血管生成以及控制实体癌的生长和转移提供更好的见解。
