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Introduction: Leukemia is a global health concern that requires alternative treatments due to the limitations of the FDA-approved drugs. Our focus is on p53, a crucial tumor suppressor that regulates cell division. It appears possible to stabilize p53 without causing damage to DNA by investigating dual-acting inhibitors that target both ligases. The paper aims to identify small molecule modulators of Mdm2 and Pirh2 by using 3D structural models of p53 residues and to further carry out the synthesis and evaluation of hit candidates for anti-cancer potency by in vitro and in silico studies. Methods: We synthesized structural analogues of MMs02943764 and MMs03738126 using a 4,5-(substituted) 1,2,4-triazole-3-thiols with 2-chloro N-phenylacetamide in acetone with derivatives of PAA and PCA were followed. Cytotoxicity assays, including MTT, Trypan Blue Exclusion, and MTS assays, were performed on cancer cell lines. Anti-proliferation activity was evaluated using K562 cells. Cell cycle analysis and protein expression studies of p53, Mdm2, and Pirh2 were conducted using flow cytometry. Results: As for results obtained from our previous studies MMs02943764, and MMs03738126 were selected among the best-fit hit molecules whose structural analogues were further subjected to molecular docking and dynamic simulation. Synthesized compounds exhibited potent anti-proliferative effects, with PAC showing significant cytotoxicity against leukemia cells. PAC induced cell cycle arrest and modulated p53, Mdm2, and Pirh2 protein expressions in K562 cells. Molecular docking revealed strong binding affinity of PAC to p53 protein, further confirmed by molecular dynamics simulation. Discussion: The study presents novel anticancer compounds targeting the p53 ubiquitination pathway, exemplified by PAC. Future perspectives involve further optimization and preclinical studies to validate PAC's potential as an effective anticancer therapy. [ABSTRACT FROM AUTHOR]

In this investigation, we successfully synthesized bismuth oxide (Bi2O3) nanoparticles (NPs) via simple combustion method using Artocarpous heterophyllus (Jackfruit) extract as fuel. Both α and β polymorphs of bismuth oxide NPs was prepared using same Artocarpous heterophyllus fuel but there is a variation in the addition of fuel in the range of 1 mL–6 mL. The prepared NPs were characterized by utilizing spectroscopic techniques. The photocatalytic efficiencies were found to be 84 %, 93 % for both α, β forms respectively. Methylene blue dye exhibits effective degradation for β‐phase compared to α‐phase. Furthermore, Electrochemical impedance spectroscopy and sensing (CV) activities were performed. The bismuth oxide modified electrodes exhibits better sensing activity towards dopamine, ascorbic acid, lead nitrate, and results obtained from EIS data revealed the super capacitor characteristics of Bi2O3 nanoparticles. This extensive investigation assessed the effectiveness of Aspergillus Niger‐fighting drugs, as well as the antibacterial effects of synthesized nanoparticles on Staphylococcus Aureus and Escherichia Coli. Measurements of optical density were used to establish the MIC values for antifungals. The protein 4XUY has a strong binding affinity of −6.4 Kcal/mol, with four important hydrogen bond interactions (LYS51, HIS84, ASN131, and GLU238) revealed by molecular docking research. These results expand our knowledge of the therapeutic uses of bismuth oxide nanoparticles by highlighting their potential as effective antibacterial agents and by providing insightful information about how they work against pathogenic microorganisms. [ABSTRACT FROM AUTHOR]