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

Sadaqat Ali; Asifa Noreen; Adeem Qamar; Imran Zafar; Quratul Ain; Hiba-Allah Nafidi; Yousef A Bin Jardan; Mohammed Bourhia; Summya Rashid; Rohit Sharma

doi:10.3389/fchem.2023.1174363

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

Front Chem. 2023 Apr 26:11:1174363. doi: 10.3389/fchem.2023.1174363. eCollection 2023.

Authors

Affiliations

¹ Medical Department, DHQ Hospital Bhawalnagr, Punjab, Pakistan.
² Department of Chemistry, Rippha International University, Faisalabad, Pakistan.
³ Department of Pathology, Sahiwal Medical College Sahiwal, Punjab, Pakistan.
⁴ Department of Bioinformatics and Computational Biology, Virtual University of Pakistan, Punjab, Pakistan.
⁵ Department of Chemistry, Government College Women University, Faisalabad, Pakistan.
⁶ Department of Food Science, Faculty of Agricultural and Food Sciences, Laval University, Quebec City, QC, Canada.
⁷ Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
⁸ Laboratory of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune, Morocco.
⁹ Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

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.

Keywords: Amomum subulatum; TP53; anti-cancer compounds; bioinformatics; cancer; high-throughput techniques; pharmacophore modeling.