Introduction

The marine environment has contained an enormous amount of valuable nutritive food additives, especially the seaweeds, are immensity source of various vitamins like A, E, C, D, B, B12, folic acid, niacin, riboflavin, pantothenic acid and minerals such as Calcium, Potassium, Sodium and Phosphorus (Subathraa & Poonguzhali, 2013). There are many numbers of bioactive substances are naturally present in marine flora which includes flavonoids, Terpenoids, Saponins, Phenols, oxygen heterocyclics, Carbohydrate, nitrogen heterocyclics, Proteins, Tannins, Oils, Resins and Aminoacids, Alkaloids, etc. These are the phytochemical compounds that are enhancing the antibacterial and anticancer properties of corresponding floras that would fight against various foreign agents and balance the internal environment (Krish & Das, 2014).

There are 18 species of Chlorophyceae, 25 species of Phaeophyceae and 39 species of Rhodophyceae has contained an antibacterial and antifungal activity that were experimentally proven by past decades (Salvador, Garreta, Lavelli, & Ribera, 2007). The previous researches support the fact that an abundance of cytotoxicity capacity and insecticide activity arise in marine floral organisms. The following list of seaweeds is few instances for an above statement, such as Ulva fasciata, Sargassumlanceolatum, Dictyotahauckiana, Iyengariastellata, Melanothamnusafaqhusainii, Dictyotadichotoma var. velutricata, Dictyotaindica, Jolynalaminarioides, Sargassumilicifolium (Ayesha, Hira, Sultana, Jehan, & Ara, 2010). Algal species are a good alternative for allopathic medicines and help in designing new drugs in pharmaceutical industries.

The present investigation was aimed to explore the anticancer potential of D. bartayresianain insilico analysis. Dictyotabartayresiana Lamour (D. bartayresiana) belongs to the family Dictyotaceae; class Phaeohyceae; order Dictyotales. They are predominantly inhabitsin tropical and subtropical regions which have contained extremely rich amount of secondary metabolites with enormous biological activity especially these metabolites helps to act as a biological agent for antioxidant, antiviral, antifungal activities and antimicrobial activities (Chew, Lim, Omar, & Khoo, 2008).

Morphological features

D. bartayresiana has 8-20 cm thalli, which are attached by many patches of minute rhizoids, straps length measured at 10-15 cm long, 5.7-7.3 mm wide, branching angle noted in 70-80°, straw-colored confirms the species belongs to brown algae group. Strap surfaces have four sporangia on both sides, but gametangial and sterile cells are not known. Hair tufts are a common structure in water inhabitant plants and surface proliferation absent, but margins are smooth.

The current research paved the way to design drugs from D. bartayresiana lamour with the help of computational methods. The designed compounds have involves the following reactions such as assimilation, delivery, anabolism, catabolism, emission and toxic effect. These processes are essential pathways for a typical drug that can be easily understood by computational methods. The main target of the computational method is to establish the desired property of drugs and avoiding following unwanted things like toxic content, a sudden inactive state in response to the physical environment, the reaction on valuable compounds and so on. Molecular modeling studies are considered a good alternative for laboratory testing, which consumes less time and produces significant results. The molecular docking simulation effect transfers 10% of pharmaceutical R & D expenditure into 20% by 2016 (Waterbeemd & Gifford, 2003).

The importance of Molecular studies and molecular modeling helps to give strong evidence over biological experiments and understanding the interactions between target receptors and designed molecules. The present study involves Hexadecane, Hexadecanoic acid methyl ester and Quinoline, 1,2-dihydro-2,2,4-trimethyl) identified by GC-MS study were subjected to molecular docking for better recognition of their interaction with Vascular endothelial growth factor receptor 1 (VEGFR 1) and compared with standard as 5-fluorouracil.

Methodology

Ligand

Ligands for our study included Hexadecane, Hexadecanoic acid methyl ester, Quinoline, 1,2-dihydro-2,2,4-trimethyl) and 5-fluorouracil used as standard. The structures and physicochemical properties of these compounds were retrieved from the PubChem database (www.ncbi.nlm.gov/pubchem), NIST and SDBS databases, which makes database search for a broad range of properties including compound structure, name, fragments, molecular weight, chemical formula, hydrogen bond donor and acceptor count. It has its own online editor with smiles (Simplified Molecular Input Line Entry Specification) format and our compounds are converted to pdf format using this converter. Lipinski's properties, such as molecular weight and number of hydrogen bond donors and acceptors, were taken from the PubChem. Table 2; Table 1 represent the details of target ligands and protein. Figure 1 shows the structure of the ligands.

Protein

The RCSB PDB (Research Collaboratory for Structural Bioinformatics, Protein Data Bank) is a repository for the 3D structural data of large biological macromolecules such as proteins and nucleic acids. It provides simple and advanced searches based on annotations related to sequence, structure and function. The three-dimensional protein structure of the vascular endothelial growth factor receptor one was given in Figure 2. The crystal structure of the drug target Vascular endothelial growth factor receptor one was downloaded from the Protein Data Bank (PDB ID: 3HNG) for Colon cancer (http://www.pdb.org).

In Silico Docking Studies

The following two databases are repository units of storing an enormous amount of Protein and ligand structures in an available format such as protein data bank (PDB) database and Pubchem. Docking studies have involved a basic fundamental process including docking score calculation, framing of the grids and binding of activators into targeted proteins, which were done by using the autodock tool. The ChemDraw software helps to evaluate the energy minimization capacity of the resulting compound. Energy minimization is a vital step for understanding the potentiality of ligand to conquers the targeted protein. To get the purpose, the hetero atoms consisting of water molecules and other extra atoms were removed from the proteins. A Lamarckian genetic algorithm method, implemented in the program Auto Dock 4.1, was employed. The Autodock software plays an important role in the determination of energy during the contact of the ligand pose with the protein under minimum energy concentration. As per the genetic algorithm, all the torsions were allowed to rotate during docking. In the protein center, the place has a grid map which formulated by Auto Grid. The Lamarckian genetic algorithm and the pseudo-Solis and Wets methods were implemented for minimization, using default parameters (Ghose & Crippen, 1987; Shruthi, Rai, & Ramachandra, 2013). Complex structures were modeled using modeling software’s Pymol (2.2 version, Delano Scientific LLC, San Carlos, CA, USA), Pyrx virtual screening software 0.8, Chimera (1.10.1 version UCSF Resources for biocomputing visualization and informatics, NIH, CA, USA) and Pose view (Olson & J, 2010) installed on a desktop equipped with Pentium (R) Dual-E6600 at 3.05 GHz 3.06 GHz processor (2 GB RAM Core CPU) running the Ubuntu 12.01 (LINUX) and Windows (Windows 8, 64bit) operating system.

Results and Discussion

The ligand molecules were selected by their docking energy and good interaction with the active site residues and the results are shown in Table 4; Table 3; Table 2. Hydrogen bond was indicated by violating color lines in between atoms involved and the rest of the interactions were hydrophobic. The activation energy of Hexadecane was found to be -6.20 kcal/mol. The hexadecanoic acid methyl ester was found to be -6.60 Kcal/mol, Quinoline, 1,2-dihydro-2,2,4-trimethyl was found to be -6.60 Kcal/mol and 5-fluorouracil used as a standard was found be -5.10 Kcal/mol. The molecular docking of the hits showed the binding mode and interaction energy. The h-bond pattern was analyzed and confirmed the activation of target protein 3HNG to show the anti-colon cancer activity of Hexadecane, Hexadecanoic acid methyl ester, Quinoline, 1,2-dihydro-2,2,4-trimethyl. Among the various compounds, Hexadecanoic acid methyl ester and Quinoline, 1,2-dihydro-2,2,4-trimethyl has greater binding energy than standard. Figure 6; Figure 5; Figure 4; Figure 3 show the interaction of ligands and protein shows the cartoon, 2D view and 3D surface view.

The colon cancer (CC) is one of the widespread malignancies which severely cause mortality than other cancer-related cases that reported from WHO. The colon cancer has been taken off the people's life averagely one million per year and the process of initiation, development, progression and invasion not clearly understood to date (Muzny et al., 2012). The prevention of colon cancer is the main target for saving people's lives from the terrible disease. 5-fluorouracil used as standard chemotherapy for colon cancer suggested by the national cancer institute. In silico approaches are not only encouraging in disclosing the complex nature of changes in genetic activity during colon carcinogenesis but also help in the information database, which may be useful for identifying novel therapeutic targets.

Molecular Docking has to enhance the innovative research by depicting the binding affinity of targeted protein with ligands. The formation of the complex is the main expected outcome of docking studies and the complex has to maintain stability with the highest concentration (Sandeep, Nagasree, Hanisha, & Kumar, 2011). Recent researchers are using this technique for inventing new drugs for their drug discovery process and the computational method reveals the exact capacity of molecules interaction for further research (Koppen, 2009). The pharmaceutical industry encourages structure-based drug design by docking tools because of the reliable results of binding affinity and receptor binding sites (Cosconati et al., 2010; Seeliger & Groot, 2010).

Cancer treatment involves either suppressing tumor growth or completely terminate the growth mass. The stimulation of natural cell death has a promising method for all cancers treatment and considered as non-invasive therapy. The advantage of eliciting apoptosis is not only specific to single cancer but also almost all cancers. Recent research supports the apoptosis process and the main target for anticancer therapy (Pfeffer & Singh, 2018).

Phytochemicals are extensively and effectively used in the treatment of various diseases in conventional medicinal treatment. The treatment of chronic diseases like cancer with phytochemicals is critical in the research studies (Ali et al., 2016). Our in silico approach on phytochemicals Hexadecane, Hexadecanoic acid methyl ester, Quinoline, 1,2-dihydro-2,2,4-trimethyl against colon cancer target protein Vascular Endothelial Growth Factor 1 (3HNG) is carried out using virtual screening, molecular docking and ADMET methods. Virtual screening of Hexadecane, Hexadecanoic acid methyl ester, Quinoline, 1,2-dihydro-2,2,4-trimethyl and 5-fluorouracil used as standard compound showed the binding affinity towards target 3HNG. The compound was screened with binding affinity and the compound was selected as hits.

VEGF, commonly known as a vascular endothelial growth factor, is a key point formation of tumors and later become angiogenesis. In colon cancer consists of abundant malignant tumor which elicits from VEGF. The angiogenesis is a process that formed due to tumor growth and metastasis. Evidence from preclinical and clinical study indicates Vascular endothelial growth factor is the major angiogenic factor in human colon cancer that coupled with the arrangement of metastases and poor prognosis (Ellis, 2000). Several studies have implicated VEGF in human colon cancer angiogenesis (Brown et al., 1992). VEGF receptor-1 (VEGFR-1) is a high-affinity receptor for VEGF and is normally considered specific to colon cancer (Fan et al., 2005).

The activation energy of Hexadecane, Hexadecanoic acid methyl ester, Quinoline, 1,2-dihydro-2,2,4-trimethyl and 5-fluorouracil was found be -6.20 Kcal/mol, -6.60 Kcal/mol, -6.60 Kcal/mol and -5.10 Kcal/mol respectively. Among the various compounds, Hexadecanoic acid methyl ester and Quinoline, 1,2-dihydro-2,2,4-trimethyl) has potential activity than standard. The docking studies of Hexadecane, Hexadecanoic acid methyl ester, and Quinoline, 1,2-dihydro-2,2,4-trimethyl confirmed the suppression of target protein Vascular endothelial growth factor receptor 1 (VEGFR 1) to show the anti-colon cancer activity.

Conclusions

The molecular docking studies are one of the most influential techniques to find out new ligand for known protein and facilitates in treating dreadful diseases. In this present work, we have carried out molecular docking to analyze the binding properties of the mediator called 3HNG with Hexadecane, Hexadecanoic acid methyl ester, Quinoline, 1,2-dihydro-2,2,4-trimethyl) reported from Dictyotabartayresiana and 5-fluorouracil used as standard. The wet analysis carried out by us showed the best result with 3HNG and proven anti-colon cancer property. Among the various compound, of Hexadecanoic acid methyl ester and Quinoline, 1,2-dihydro-2,2,4-trimethyl) has higher binding energy than standard. So the present study may strongly conclude that anti-colon cancer property of the seaweed extract.