Natural Compounds as Potential Inhibitors of PIK3CG for the Management of Triple-Negative Breast Cancer: A Biocomputational Study

Abstract

Triple negative breast cancer (TNBC) an aggressive and diverse subtype of breast cancer. Lack of three crucial receptors estrogen, progesterone, and HER2 expression make untreatable now yet, many approaches utilized but no satisfactory results came to manage TNBC. In numbers of treatments strategy chemotherapy, a promising option, while chemoresistance major challenge. In this study, we investigated natural compounds as possible inhibitors of PI3KG, a crucial protein associated with cancer growth and therapy resistance. Molecular docking research revealed that all five tested natural compounds exhibited enhanced binding affinity for PI3KG. Among them Phosmidosine B had the highest affinity, with a docking score of -10.01 kcal/mol and a Glide energy of -60.45 kcal/mol. Emodacidamide E (9.69 kcal/mol; -56.91 kcal/mol), Emodacidamide H (-9.62 kcal/mol; -52.49 kcal/mol), Methylinoscavin D (-9.57 kcal/mol; -58.71 kcal/mol), and 1-hydroxymethyl-8-hydroxy-anthraquinone-3-carboxylic acid (-9.54 kcal/mol; -43.78 kcal/mol) followed. ADME analysis and cytotoxicity prediction showed that all of the chosen compounds had good drug like attributes and safety profiles, which supports their drug properties and low toxicity potential. In conclusion, the significant binding affinities, stable interaction energies, and good ADME and cytotoxicity profiles of these natural compounds, show that they could be good PI3KG inhibitors. Nevertheless, extensive experimental validation is essential to facilitate their further therapeutic advancement.

Keywords: Cytotoxicity profiles, PIK3G, Structural based virtual screening, Triple negative breast cancer, Natural compounds.

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