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. 2022 Jul 1;23(7):2421-2430.
doi: 10.31557/APJCP.2022.23.7.2421.

Molecular Docking and in silico Pharmacological Screening of Oleosin from Cocos Nucifera Complexed with Tamoxifen in Developing Potential Breast Chemotherapeutic Leads

Janeea Myles D Dela Cruz  1 , Sophia Allison A Dones  1 , Rianne C Villanueva  1 , Alexis M Labrador  1 , Myla R Santiago-Bautista  1   2
Affiliations

Molecular Docking and in silico Pharmacological Screening of Oleosin from Cocos Nucifera Complexed with Tamoxifen in Developing Potential Breast Chemotherapeutic Leads

Janeea Myles D Dela Cruz et al. Asian Pac J Cancer Prev. .

Abstract

Objective: Tamoxifen is a widely used drug for breast cancer therapy; however, concerns and controversies regarding its efficiency arise as it induces various side effects, including endometrial cancer. This study aimed to assess the application of Oleosin as a potential protein carrier of Tamoxifen by evaluating the pharmacokinetic and pharmacological properties of Tamoxifen and determining its intermolecular interactions with Oleosin through in silico techniques.

Methods: The pharmacokinetic and pharmacological properties of Tamoxifen were assessed by using predictive applications such as SwissADME, PaccMann, and Way2Drug. On the other hand, Oleosin does not have a crystal structure in PDB. Thus, homology modeling was done through SWISS-MODEL to obtain a structure. The interactions between Oleosin (Accession no.: AZZ09171.1) and Tamoxifen (PubChem ID: 2733526) were studied by performing molecular docking using AutoDock4 to determine their feasibility as breast cancer drug combinations.

Result: The chosen structure of Oleosin from the homology modeling resulted in an RMSD of 1.80Å. Tamoxifen was predicted to have the highest activity in MCF7 cell lines, direct interaction with cytochrome enzymes, mediated interaction with estrogen receptors and tyrosine-protein kinase FYN, and low toxicity hazards based on the acute rat toxicity assay. It has lowest binding affinity of -5.26 kcal/mol. The hydrophobic (Ala106, Leu77, Ile80, Val84, and Tyr81) and electrically charged (Lys107 and Asp108) amino acids were critical in binding in the Oleosin-Tamoxifen-complex. Heatmap revealed that phenyl, ether, amine, and alkenyl are the functional groups involved in the receptor-ligand interactions.

Conclusion: The application of Oleosin as a potential drug carrier was demonstrated by assessing the intermolecular interactions between the Tamoxifen and Oleosin through molecular docking. The properties of Tamoxifen revealed that the molecular targets impact the efficiency and the mechanism of action of the drug. This can also be the basis for investigating and determining the serious adverse effects induced by the drug.

Keywords: Estrogen Receptor; Molecular docking; Oleosin; Tamoxifen; breast cancer.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
BOILED-Egg Model of Tamoxifen. The yellow or the yolk represents the Blood-Brain Barrier. The white area represents human gastrointestinal absorption (HIA)
Figure 2
Figure 2
The ADME Results of Tamoxifen. This includes the (A) Physicochemical properties, (B) Lipophilicity, (C) Water Solubility, (D) Pharmacokinetics, (E) Druglikeness, and (F) Medicinal Chemistry
Figure 3
Figure 3
The Bioavailability Radar of Tamoxifen
Figure 4
Figure 4
Results of Homology Modeling from SWISS-MODEL. (A) 3D/Crystal structure of Oleosin. (B) Information about the structure of the generated model. (C) and (D) Ramachandran plots of the model. The 3D model of Oleosin from chain B of Epstein-Barr viral Bcl-2 protein was selected as it produced an acceptable value of sequence identity, sequence similarity, molecule size, and is Ramachandran favored
Figure 5
Figure 5
Predicted Molecular Interactions of Tamoxifen with Oleosin based on PaccMann Webserver and AutoDock 4.0 software.(A) Heatmap of Tamoxifen from PaccMann. Results showed the most and least interactive functional groups of Tamoxifen based on the intensity of the colors. Docking results from AutoDock 4 and BIOVIA Discovery Studio. (B) the best docking pose of Tamoxifen. (C) Close-up 3D visualization of Tamoxifen and Oleosin interaction. (D) 2D diagram of the receptor-ligand interaction with the formed bonds. Oleosin and Tamoxifen were successfully docked with -5.26 kcal/mol binding energy
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