Unveiling the oncological inhibition of bioactive compounds from Adansonia digitata via in silico analysis by targeting γ-butyrobetaine dioxygenase 1 against triple negative breast cancer

Adansonia digitata extracts are well known for their wide range of nutritional and medicinal benefits, including anti-diabetic, anti-inflammatory, antioxidant, and anti-cancerous properties. Yet, its efficacy against breast cancer has not been well-studied so far. Hence this study aims to investigate the anti-cancer properties of phytochemicals from the bark extract of the Adansonia digitata tree against BBOX1, a protein that stimulates the growth of Triple Negative Breast Cancer (TNBC) cells. TNBC is a highly aggressive and fatal form of cancer with limited therapeutic options available. By incorporating computational bioinformatics including Molecular docking, MMGBSA/PBSA, Molecular dynamics, and PCA/FEL analysis, the phytocompounds were scrutinized against BBOX1. Among 274 Phytocompounds only 37 compounds with good pharmacokinetic profiles based on ADME analysis were selected and docked with BBOX1. Of these compounds, the top 6 phytocompounds (CID_22217550, CID_559476, CID_6423866, CID_595387, CID_550931, and CID_559495) demonstrated good binding affinity, with better docking scores ranging from -8.599 to -7.207 kcal/mol respectively. Furthermore, based on MM/GBSA, Interaction profiling, and DFT analysis, only three phytocompounds namely CID_22217550, CID_559476, and CID_550931 were found to interact with the key residues such as Tyr_177, Trp_181, Asp_191, and Tyr_366 with better binding efficacy. In addition, these compounds were also observed to have the least RMS deviations with stable H-bond interactions maintained throughout the MD production run. Henceforth, the overall analysis infers that the phytocompounds CID_22217550, CID_559476, and CID_550931 shall act as potent inhibitors of BBOX1. However, their inhibitory efficacy has be to analyzed with further in vitro and in vivo analysis.