In Silico Screening of Marine Compounds as an Emerging and Promising Approach against Estrogen Receptor Alpha-Positive Breast Cancer

• Published in: BioMed research international 2021-12, Vol.2021, p.9734279-7
• Main Authors: Alamri, Abdulwahab, Rauf, Abdur, Khalil, Anees Ahmed, Alghamdi, Adel, Alafnan, Ahmed, Alshammari, Abdulrahman, Alshammari, Farhan, Malik, Jonaid Ahmed, Anwar, Sirajudheen
• Format: Article
• Language: English
• Subjects: Analysis; Antineoplastic Agents - pharmacology; Binding energy; Binding sites; Bioavailability; Biological Products - pharmacology; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Cancer; Cancer therapies; Care and treatment; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Datasets; Diagnosis; Docking; Early Detection of Cancer - methods; Energy; Enzymes; Epidermal growth factor; Epidermal growth factor receptors; ErbB-2 protein; Estrogen; Estrogen Receptor alpha - metabolism; Estrogen receptors; Estrogens; Experimental research; Female; Free energy; Growth factor receptors; Growth factors; Health aspects; Heat shock proteins; Hsp90 protein; Humans; Inhibitors; Lead compounds; Ligands; Marine Biology; Molecular Docking Simulation; Molecular Dynamics Simulation; Mortality; Prevention; Proteins; Receptor, ErbB-2 - metabolism; Receptors; Risk factors; Screening; Tumors; Uterus; Womens health
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2021/9734279

Presently, the majority of breast tumors are estrogen receptor (ER) positive. Breast cancer (BC) is defined by uncontrolled cell proliferation (CP) in breast tissue. BCs are caused by the overexpression of genes that promote CP in breast cells. The discovery of effective inhibitors is an excellent chemopreventive method. Our in silico approach analysis offers a pharmacoinformatics methodology for identifying lead molecules targeting cochaperone HSP90 and the epidermal growth factor receptors (EGFR) and human epidermal growth factor receptor 2 (HER2)/neu receptor. BC has been associated with the high expression of these targets. The use of drug-likeness filters aided in determining the therapeutic properties of possible lead compounds. In this study, docking-based virtual screening (VS) was performed. Database of about 450 cancer marine compounds was used. The X-ray-assisted structure of ERα with 4-OHT (PDB code: 3ERT) was chosen for 4-OHT. A docking-based virtual screening was performed on the dataset supplied using the molecular operating environment (MOE) dock application. The binding energy (BE) and explanation of the protein inhibitor interaction (PII) are crucial findings for future both in terms of dry or wet lab research. The GBVI/WAS binding-free energy assessment (in kcal/mol) scores were used to grade the compounds. Compounds with a BE of less than -9.500 kcal/mol were deemed to be the most effective inhibitors. For further analysis, the top seven structurally diverse scaffolds were selected. Seven marine compounds exhibited the best docking score, which validates them to be potent anti-BC compounds. These compounds’ bioactive potential and prospective drug-likeness profile make them promising leads for further experimental research.