Structure Based Multitargeted Molecular Docking Analysis of Selected Furanocoumarins against Breast Cancer

• Published in: Scientific reports Vol. 9; no. 1; pp. 15743 - 13
• Main Authors: Acharya, Reetuparna, Chacko, Shinu, Bose, Pritha, Lapenna, Antonio, Pattanayak, Shakti Prasad
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31-10-2019; Nature Publishing Group
• Subjects: 13/95; 631/67; 631/67/1347; 692/4028/67/1347; Antagonists; Binding Sites; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer therapies; Catalytic Domain; Drug Design; Drug development; Epidermal growth factor receptors; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - metabolism; Estrogen Receptor alpha - antagonists & inhibitors; Estrogen Receptor alpha - metabolism; Female; Furanocoumarins; Furocoumarins - chemistry; Furocoumarins - metabolism; Furocoumarins - therapeutic use; Humanities and Social Sciences; Humans; Ligands; MCF-7 Cells; Menopause; Molecular Docking Simulation; Monoclonal antibodies; multidisciplinary; Paclitaxel; Psoralen; Science; Science (multidisciplinary); Tamoxifen; Targeted cancer therapy; TOR protein; TOR Serine-Threonine Kinases - antagonists & inhibitors; TOR Serine-Threonine Kinases - metabolism; Trastuzumab
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-52162-0

Breast cancer is one of the biggest global dilemmas and its current therapy is to target the hormone receptors by the use of partial agonists/antagonists. Potent drugs for breast cancer treatment are Tamoxifen, Trastuzumab, Paclitaxel, etc. which show adverse effects and resistance in patients. The aim of the study has been on certain phytochemicals which has potent actions on ERα, PR, EGFR and mTOR inhibition. The current study is performed by the use of molecular docking as protein-ligand interactions play a vital role in drug design. The 3D structures of ERα, PR, EGFR and mTOR were obtained from the protein data bank and docked with 23 3D PubChem structures of furanocoumarin compounds using FlexX. Drug-likeness property was checked by applying the Lipinski’s rule of five on the furanocoumarins to evaluate anti-breast cancer activity. Antagonist and inhibition assay of ERα, EGFR and mTOR respectively has been performed using appropriate
in-vitro
techniques. The results confirm that Xanthotoxol has the best docking score for breast cancer followed by Bergapten, Angelicin, Psoralen and Isoimperatorin. Further, the
in-vitro
results also validate the molecular docking analysis. This study suggests that the selected furanocoumarins can be further investigated and evaluated for breast cancer treatment and management strategies.