Pharmacoinformatics approach for the screening of Kovidra phytoconstituents against tumor suppressor protein in triple negative breast cancer.

Globally, 2.3 million women were diagnosed with breast cancer, with 6,85000 mortalities in year 2021; making it the world's most prevalent cancer. This growing global burden necessitates a new treatment option, and plant-based medicines offers a promising alternative to conventional cancer treatment. In this work, screening of phytoconstituents of an indigenous therapeutic plant, carried out for potential regulator of tumor suppressor protein p53. Here, an analysis was employed to develop more effective, pharmaceutically potent small drug-like compounds that target tumor suppressor protein p53. The methanol and aqueous powdered extracts of were prepared and phytochemically evaluated along with antioxidant property evaluation. The LC of methanol (325.33 µg/ml) and aqueous extract (361.15 µg/ml) showed their cytotoxic characteristics. Further, GCMS analysis of both the extracts reveals total 57 secondary metabolites. Among these, four lead compounds; compound 1, compound 2, compound 3 and compound 4 were found to have the highest binding ability (-8.15 to -5.40 kcal/mol) with p53. MD simulation and binding free energy validates these findings with highest binding free energy (-67.09 ± 4.87 kcal/mol) towards p53 by the lead phytocompound 2. Selected compounds exhibit excellent pharmacokinetic features and drug-like characteristics. The acute toxicity (LD) values of the lead phytocompounds ranges from 670 mg/kg to 3100 mg/kg, with toxicity classes of IV and V. As a result, these druggable phytochemicals could serve as potential lead applicants for triple negative breast cancer treatment. However, more and research is planned to produce future breast cancer medicine. HIGHLIGHTSScreening of phytoconstituents of an indigenous therapeutic plant, , for potential regulator of tumor suppressor protein p53.The LC of methanol (325.33µg/ml) and aqueous extract (361.15µg/ml) showed their cytotoxic characteristics.GCMS analysis of both the extracts reveals total 57 secondary metabolites. Among these, four lead compounds were found to have the highest binding affinity (-8.153 to -5.401 kcal/mol) with tumor suppressor protein p53.MD simulation along with the Prime MM/GBSA binding free energy validates this discovery with highest binding free energy (-67.09 ± 4.87 kcal/mol) towards p53 by the lead compound 2.The acute toxicity (LD) values of the lead phytocompounds ranges from 670 mg/kg to 3100 mg/kg, with toxicity classes of IV and V.As a result, these druggable phytochemicals could serve as potential lead applicants for triple negative breast cancer treatment.Communicated by Ramaswamy H. Sarma.