Amomum subulatum: A treasure trove of anti-cancer compounds targeting TP53 protein using in vitro and in silico techniques

Abstract

Cancer is a primary global health concern, and researchers seek innovative approaches to combat the disease. Clinical bioinformatics and high-throughput proteomics technologies provide powerful tools to explore cancer biology. Medicinal plants are considered effective therapeutic agents, and computer-aided drug design (CAAD) is used to identify novel drug candidates from plant extracts. The tumour suppressor protein TP53 is an attractive target for drug development, given its crucial role in cancer pathogenesis. This study used a dried extract of Amomum subulatum seeds to identify phytocompounds targeting TP53 in cancer. We apply qualitative tests to determine its phytochemicals (Alkaloid, Tannin, Saponin, Phlobatinin, and Cardic glycoside), and found that alkaloid composed of 9.4% ± 0.04% and Saponin 1.9% ± 0.05% crude chemical constituent. In the results of DPPH Analysis Amomum subulatum Seeds founded antioxidant activity, and then we verified via observing methanol extract (79.82%), BHT (81.73%), and n-hexane extract (51.31%) found to be positive. For Inhibition of oxidation, we observe BHT is 90.25%, and Methanol (83.42%) has the most significant proportion of linoleic acid oxidation suppression. We used diverse bioinformatics approaches to evaluate the effect of A. subulatum seeds and their natural components on TP53. Compound-1 had the best pharmacophore match value (53.92), with others ranging from 50.75 to 53.92. Our docking result shows the top three natural compounds had the highest binding energies (−11.10 to −10.3 kcal/mol). The highest binding energies (−10.9 to −9.2 kcal/mol) compound bonded to significant sections in the target protein’s active domains with TP53. Based on virtual screening, we select top phytocompounds for targets which highly fit based on pharmacophore score and observe these compounds exhibited potent antioxidant activity and inhibited cancer cell inflammation in the TP53 pathway. Molecular Dynamics (MD) simulations indicated that the ligand was bound to the protein with some significant conformational changes in the protein structure. This study provides novel insights into the development of innovative drugs for the treatment of cancer disorders.

Nanoengineered chitosan functionalized titanium dioxide biohybrids for bacterial infections and cancer therapy

“…At 382 nm, near-band edge (UV emission) was detected due to exciton-exciton recombination processes; two blue emission peaks were identified at 437 and 482 nm because of oxygen vacancies and self-trapped Ti interstitials 54 . A photo-generated hole and an ionized electron in the valence band of TiO 2 recombine, resulting in a green emission peak at 517 nm 35 . To produce free radicals, which play a part in biological performance, these oxygen vacancies and self-trapped Ti interstitials.…”

“…One of the traditional seeds Amomum subulatum belonging to the Zingiberaceae family used as a curative and preventive drug for digestive disorders, lung congestion, and mouth infections owing to their essential oil constituents which majorly consist of 1,8-cineole followed by α-terpineol as well as as limonene etc. In addition, the seed has cancer prevention, anti-bacterial, and antioxidant properties that improve aroma 35 , 36 . Chitosan is a naturally derived product that can be applied in different areas due to its biocompatibility, biodegradability, and benign properties 37 .…”

Cauchy hyper-graph Laplacian nonnegative matrix factorization for single-cell RNA-sequencing data analysis

“…High-dimensional data may be handled with NMF [ 15 ], which denotes the number of genes and samples, respectively, in a non-negative matrix of dimensions. The goal of NMF is to identify two non-negative matrices that meet two requirements [ 16 ].…”

“…Clustering is a common method to analyze gene expression data [ 13 ]. Traditional clustering techniques include K-means and spectral clustering (SC), among others [ 14 , 15 ]. The efficacy of conventional clustering approaches is significantly impacted by the high dimension, high noise, and high sparsity of single-cell RNA-seq data.…”

In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer

“…Drug design techniques, such as molecular docking and molecular dynamic simulations, have been used to study DNA binding and stability in solvents ( Ali et al, 2023c ). The new most dynamic scoring, particularly with molecular mechanics/Poisson−Boltzmann surface area (MM/PBSA) and QM/MM (quantum mechanics/molecular mechanics), has reduced false positives in virtual screening ( Parves et al, 2023 ).…”