An in-silico investigation and network pharmacology based approach to explore the anti-breast-cancer potential of Tecteria coadunata (Wall.) C. Chr.

Uncontrolled cell proliferation is a common definition of cancer. After lung carcinoma, breast neoplasm is the second-most prevalent kind of cancer. The majority of breast cancer cells and healthy breast cells both have receptors for circulating oestrogen and progesterone. In order to promote the development and division of cancer cells, oestrogen and progesterone bind to the receptors and may collaborate with growth factors (such as oncogenes and mutant tumour suppressor genes). As per the literature, Tecteria coadunata (Wall.) C. Chr. has anticancer, antioxidant and anti-inflammatory potential. After the hydroalcoholic extraction of this rhizome, total of 200 phytochemicals were retrieved from HR-LCMS analysis. In this current study, Network pharmacology was carried out to explore the rationale of Tecteria coadunata (Wall.) C. Chr. by using different database using Cytoscape software. The network depicted the interaction of Bioactives with their targets and their association with several disease, especially breast cancer. Tecteria coadunata (Wall.) C. Chr. has offered new relationship with variety of genes and its applications in different types of breast cancers. Further Gene Ontology was carried out and it showed key targets were TP53, BRCA2, PGR and CHEK 2. Further Signalling pathways were also enriched. Flex-X software was used for molecular docking studies, and it verified that Dopaxanthin, Dantrolene and Orotidin shows the highest binding affinities with key targets. Additionally, Pharmacokinetic analysis revealed that all top three lead compounds which follows the Lipinski Rule (Rule of three) without interrupting the conditions of bioavailability with minimal toxicity.Communicated by Ramaswamy H. Sarma.

Pharmacoinformatics approach for the screening of Kovidra (Bauhinia variegata) 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, Bauhinia variegata carried out for potential regulator of tumor suppressor protein p53. Here, an in-silico 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 Bauhinia variegata were prepared and phytochemically evaluated along with antioxidant property evaluation. The LC50 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 (LD50) 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 in vitro and in vivo research is planned to produce future breast cancer medicine. HIGHLIGHTSScreening of phytoconstituents of an indigenous therapeutic plant, Bauhinia variegata, for potential regulator of tumor suppressor protein p53.The LC50 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 (LD50) 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.

GC-MS profiling of Bauhinia variegata major phytoconstituents with computational identification of potential lead inhibitors of SARS-CoV-2 Mpro.

Severe acute respiratory syndrome coronavirus 2 was originally identified in Wuhan city of China in December 2019 and it spread rapidly throughout the globe, causing a threat to human life. Since targeted therapies are deficient, scientists all over the world have an opportunity to develop novel drug therapies to combat COVID-19. After the declaration of a global medical emergency, it was established that the Food and Drug Administration (FDA) could permit the use of emergency testing, treatments, and vaccines to decrease suffering, and loss of life, and restore the nation's health and security. The FDA has approved the use of remdesivir and its analogs as an antiviral medication, to treat COVID-19. The primary protease of SARS-CoV-2, which has the potential to regulate coronavirus proliferation, has been a viable target for the discovery of medicines against SARS-CoV-2. The present research deals with the in silico technique to screen phytocompounds from a traditional medicinal plant, Bauhinia variegata for potential inhibitors of the SARS-CoV-2 main protease. Dried leaves of the plant B. variegata were used to prepare aqueous and methanol extract and the constituents were analyzed using the GC-MS technique. A total of 57 compounds were retrieved from the aqueous and methanol extract analysis. Among these, three lead compounds (2,5 dimethyl 1-H Pyrrole, 2,3 diphenyl cyclopropyl methyl phenyl sulphoxide, and Benzonitrile m phenethyl) were shown to have the highest binding affinity (-5.719 to -5.580 kcal/mol) towards SARS-CoV-2 Mpro. The post MD simulation results also revealed the favorable confirmation and stability of the selected lead compounds with Mpro as per trajectory analysis. The Prime MM/GBSA binding free energy supports this finding, the top lead compound 2,3 diphenyl cyclopropyl methyl phenyl sulphoxide showed high binding free energy (-64.377 ± 5.24 kcal/mol) towards Mpro which reflects the binding stability of the molecule with Mpro. The binding free energy of the complexes was strongly influenced by His, Gln, and Glu residues. All of the molecules chosen are found to have strong pharmacokinetic characteristics and show drug-likeness properties. The lead compounds present acute toxicity (LD50) values ranging from 670 mg/kg to 2500 mg/kg; with toxicity classifications of 4 and 5 classes. Thus, these compounds could behave as probable lead candidates for treatment against SARS-CoV-2. However further in vitro and in vivo studies are required for the development of medication against SARS-CoV-2.