Despite the rapid developments and advancements to improve treatments, Breast cancer remains one of the deadliest health challenges and the most frequently diagnosed tumor. One of the major problems with treatment is the unique difference that each cancerous cell exhibits. As a result, treatment of breast cancer has now become more personalized based on the specific features of the tumor such as overexpression of growth factor receptors (Epidermal growth factor receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2)), hormone receptors (Human Estrogen receptor alpha (ER)) and kinases involved in pivotal signaling associated with growth (Phosphatidylinositol 3-kinase (PI3K)). Several chemotherapeutic agents have been developed to curb the menace, but the associated adverse drug effects cannot be overlooked. To this end, this study employed a molecular modeling approach to identify novel compounds of natural origin that can potentially antagonize the receptors (mentioned above) associated with the pathophysiology of breast cancer and at the same time pose very little or no side effects. The results of the molecular model of biological interactions between a library of 118 anthocyanins and the binding pockets of the protein targets identified 5 compounds (Pelargonin, Delphinidin 3-O-rutinoside, Malvin, Cyanidin-3-(6-acetylglucoside), and Peonidin 3-O-rutinoside) with good binding affinities to the protein targets. Further MM-GBSA calculations returned high binding energies. The specific molecular interactions between the compounds and the targets were analyzed and reported herein. Also, all the compounds exhibited good pharmacokinetic profiles and are therefore recommended for further analyses as they could be explored as new treatment options for a broad range and personalized breast cancer treatments.
Keywords: Breast cancer; EGFR; HER2; MM-GBSA; PI3K; estrogen receptor; molecular docking.
© The Author(s) 2022.