## 1 Introduction  
Cancer is still among the most common causes of death, and it is mostly caused by the stimulation of oncogenes and the inactivity of tumor suppressors. Over the past few years, the tumor suppressor protein p53 has evolved into an important subject in the development of anti-cancer drugs [1, 2]. Since the p53 protein was discovered in 1979, scientists have spent a great deal of time and effort investigating its importance in the spread of cancer. Fifty percent of cancer cases have been found to have either p53 protein mutations or inactivation. The protein achieves importance as a result of its involvement in cancer suppression and its capacity to react to a variety of genome-damaging stresses. p53 causes responses such as DNA reparation, apoptosis, and cell death in its wild-type form [3]. When a cell is threatened by a stress (for example, smoking or radioactivity), p53 activates several downstream pathways to guarantee that the cell maintains its normal functional state. Any time the integrity of the genome is in jeopardy, p53 steps in to protect it, earning the nickname \"guardian of the genome\" [4; 5]. The essential function played by p53 in the regulation of many cellular processes necessitates the exact management of its amount at all times. A low steady-state p53 concentration is maintained under normal conditions. p53 is negatively tuned by the murine double minute 2 (MDM2) protein, which also functions as the protein's E3 ligase [6; 7]. An auto-regulatory feedback loop is formed between p53 and MDM2, which regulate each other. MDM2 is the key component in ubiquitination-mediated degradation of p53, whereas when p53 is triggered/activated, it results in the transcription of _MDM2_ mRNA, which results in the subsequent increase of MDM2 protein [8]. A phosphate ion is bound to the p53 protein by MDM2, causing it to be degraded by the proteasome [9; 10; 11]. In several tumors, the overexpression of MDM2 is the cause of low p53 levels in many tumors, stopping key cellular processes including DNA reparation, cell cycle stoppage, and apoptosis. As a result, the presence of the protein-to-protein complex between p53 and MDM2 results in the activation and revival of the required strength of wild-type p53, which subsequently revives cell operation in the normal state via p53 moderation. Because of these factors, MDM2 is emerging as a widely utilized therapeutic strategy in cancerous cells [12; 13]. The interaction of MDM2 and p53 protein takes place through hydrophobic regions located in specific binding areas [6]. It has been discovered by studying the framework of p53 that certain tiny non-peptide molecules may imitate the complex formation sequence between p53 and MDM2. These substances may interfere with the protein-protein interaction between p53 and MDM2, resulting in an increase in the amount of p53 in the body. Blocking the protein-protein interaction via the use of these molecule inhibitors is becoming a potential treatment approach for human cancers that maintain wild-type p53 [14; 15]. In recent years, a large number of small molecule inhibitors have been identified, and several of them have passed clinical and preclinical trials. Nutlin, a class of molecular inhibitors, has a known function of binding to MDM2 such that no genotoxicity can occur. MDM2 binds to Nutlin at the pocket located at the N-terminus, which is the same pocket where p53 attaches [16; 17]. Various derivatives of Nutlin such as Nutlin-1, nutlin-2, and nutlin-3 have been discovered by [PERSON] et al., and their effects on cancer cells have been discussed in [14]. However, Nutlin-3 is the most effective compound and is commonly used in anti-cancer studies. Nutlin-3a is orally bio-available, and the preclinical data show its good anti-tumor activity, without any toxicity. Nutlin-3a has been shown to restore wild-type p53 functioning, and several additional Nutlin variations have been shown to be helpful in the treatment of tumors harboring defective or mutant p53 [18].