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. 2015 Feb 28;11(2):73-84.
doi: 10.6026/97320630011073. eCollection 2015.

In silico pharmacokinetic and molecular docking studies of small molecules derived from Indigofera aspalathoides Vahl targeting receptor tyrosine kinases

Sathish Kumar Paramashivam  1 , Kalaivani Elayaperumal  1 , Boopala Bhagavan Natarajan  1 , Manjula Devi Ramamoorthy  1 , Suganthana Balasubramanian  2 , Kannan Narayanan Dhiraviam  1
Affiliations

In silico pharmacokinetic and molecular docking studies of small molecules derived from Indigofera aspalathoides Vahl targeting receptor tyrosine kinases

Sathish Kumar Paramashivam et al. Bioinformation. .

Abstract

Angiogenesis is the formation of new blood vessels from preexisting vascular network that plays an important role in the tumor growth, invasion and metastasis. Anti-angiogenesis targeting tyrosine kinases such as vascular endothelial growth factor receptor 2 (VEGFR2) and platelet derived growth factor receptor β (PDGFRβ) constitutes a successful target for the treatment of cancer. In this work, molecular docking studies of three bioflavanoid such as indigocarpan, mucronulatol, indigocarpan diacetate and two diterpenes namely erythroxydiol X and Y derived from Indigofera aspalathoides as PDGFRβ and VEGFR2 inhibitors were performed using computational tools. The crystal structures of two target proteins were retrieved from PDB website. Among the five compounds investigated, indigocarpan exhibited potent binding energy ΔG = -7.04 kcal/mol with VEGFR2 and ΔG = -4.82 with PDGFRβ compared to commercially available anti-angiogenic drug sorafenib (positive control). Our results strongly suggested that indigocarpan is a potent angiogenesis inhibitor as ascertained by its potential interaction with VEGFR2 and PDGFRβ. This hypothesis provides a better insight to control metastasis by blocking angiogenesis.

Keywords: Angiogenesis; Autodock; Indigocarpan; Lipinski rules; PDGFRβ; VEGFR2.

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Figures

Figure 1
Figure 1
Structure of various phytoligands reported in I.aspalathoides
Figure 2
Figure 2
The three dimensional structure of selected target proteins a) VEGFR2 – 3VHE; b) PDGFRβ (Only X Chain – 3MJG)
Figure 3
Figure 3
Binding pocket identification by CASTp server. (a,c) Shows the binding sites of PDGFRβ and VEGFR2 protein respectively, and (b,d) Green color boxes highlights the amino acid residues present in the binding site.
Figure 4
Figure 4
Osiris property prediction of lead compound (Indigocarpan). It indicates that there are no toxicity risks (mutagenicity, tumorogenicity, irritating effect, reproductive effect).
Figure 5
Figure 5
Plot of Metaprint 2D predictions. Site of metabolism; the atoms in red color that most will be metabolized are colored according to the likelihood of a metabolic site; High: red, Medium: orange, Low: green, very low is not colored, and No data: grey. NOR indicates the Normalized Occurrence Ratio; a high NOR indicates a more frequently reported site of metabolism in the metabolite database.
Figure 6
Figure 6
The favorable binding portion of indigocarpan with lowest binding free energy in the ATP-binding site of VEGFR2 (PDB ID: 3VHE) as analyzed by molecular docking study. (a) 2D structure of Indigocarpan, (b) The three dimensional diagram displays the interaction of indigocarpan (the green stick) to the ATP binding site of VEGFR2 with the labeled amino acid residues CYS 919 and LYS 920 which significantly contributed to the binding. (c) The two dimensional diagram shows the interactions of indigocarpan to the amino acid residues. (d, e) denotes the binding mode of Sorafenib with VEGFR2. Similarly, colors of the residues indicate the forms of interactions as follows: van der Waals forces, green; polarity, magenta. Green arrow represents Hbonding with the amino acid main chain.
Figure 7
Figure 7
The favorable binding position of indigocarpan with lowest binding free energy of PDGFRβ (PDB ID: 3MJG) as analyzed by molecular docking study. (a) The three-dimensional diagram displays the interaction of indigocarpan (green stick) with PDGFRβ labeled amino acid residues of THR86 and THR88 which significantly contributed to the binding. (b) The two dimensional diagram shows the interactions of indigocarpan to the amino acid residues in the ATP- binding site. (c & d) denotes the binding mode of Sorafenib with PDGFRβ. Similarly, colors of the residues indicate the forms of interactions as follows: van der Waals forces, green; polarity, magenta; Green arrow represents H-bonding with the amino acid main chain.
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References

    1. Panday A, et al. J Med Chem. 2002;45:3772. - PubMed
    1. Hanahan D, Weinberg RA. Cell. 2011;144:646. - PubMed
    1. Carmeliet P, Jain RK. Nature. 2011;473:298. - PMC - PubMed
    1. Ferrara N, et al. Biochem Biophys Res Commun. 2005;333:328. - PubMed
    1. Carmeliet P, et al. Oncology. 2005;69:4. - PubMed

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