Pharmacoinformatics approach for the screening of Kovidra <i>(Bauhinia variegata)</i> phytoconstituents against tumor suppressor protein in triple negative breast cancer
Creators: name: More-Adate, Pallavi
name: Lokhande, Kiran Bharat
name: Shrivastava, Ashish
name: Doiphode, Sayali
name: Nagar, Shuchi
name: Singh, Ashutosh
name: Baheti, Akshay
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Cell Biology
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Plant Biology
subject: FOS: Biological sciences

description: 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, <i>Bauhinia variegata</i> carried out for potential regulator of tumor suppressor protein p53. Here, an <i>in-silico</i> 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 <i>Bauhinia variegata</i> were prepared and phytochemically evaluated along with antioxidant property evaluation. The LC<sub>50</sub> 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<sub>50</sub>) 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 <i>in vitro</i> and <i>in vivo</i> research is planned to produce future breast cancer medicine. 
HIGHLIGHTSScreening of phytoconstituents of an indigenous therapeutic plant, <i>Bauhinia variegata</i>, for potential regulator of tumor suppressor protein p53.The LC<sub>50</sub> 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<sub>50</sub>) 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. Screening of phytoconstituents of an indigenous therapeutic plant, <i>Bauhinia variegata</i>, for potential regulator of tumor suppressor protein p53. The LC<sub>50</sub> 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<sub>50</sub>) 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