A disease known as cancer occurs when some body cells proliferate out of control and invade other parts of the body. With trillions of cells making up the human body, cancer can begin almost anyplace. When the body needs new cells, human cells normally divide by proliferating and multiplying. New cells replace old ones when they die as a result of ageing or injury. This controlled mechanism can occasionally fail to function, causing damaged or aberrant cells to proliferate and expand when they shouldn’t. Tumours are lumps of tissue that can be formed by these cells. Cancerous or benign tumours can both occur. Malignant tumours can metastasise, or spread into, neighbouring tissues, and can also generate new tumours by travelling to far-off regions of the body. Malignant tumours are another term for cancerous tumours. Blood cancers, including leukaemias, typically do not develop into solid tumours, although many malignancies can. Benign tumours do not penetrate or spread to neighbouring tissues. Benign tumours seldom grow back after removal, while cancerous tumours occasionally do. However, benign tumours can occasionally grow to be rather enormous. Some, like benign brain tumours, are possibly deadly or cause severe symptoms. The WHO classifications serve as the basis for both cancer management and cancer diagnosis. The WHO began to incorporate biologic and molecular-genetic elements into its classifications in 2000. With the advancements in cancer genomes, these breakthroughs are having an increasingly significant impact on cancer diagnosis and treatment (1).

Cancer occurs in more than a hundred types. The organs or tissues where tumours originate are typically used to name different types of cancer. Cancers can also be classified according to the kind of cell that gave rise to them, such as squamous or epithelial cells.

Exposure to environmental contaminants, excessive alcohol use, and the use of tobacco products or betel quid (the leaf of Piper betel) and areca nut (Areca catechu) are the main risk factors for the development of human papillomavirus (HPV)-negative head and neck squamous cell cancer (HNSCC). Particularly tobacco smoke and tobacco products are high in nitrosamines and polycyclic aromatic hydrocarbons, which are recognised human carcinogens and significantly raise the risk of HNSCC. Reactive metabolites are created when carcinogens undergo metabolic activation. If these metabolites are not eliminated by detoxification, they can cause damage to DNA, usually in the form of large DNA adducts. Should the damage to the DNA be faithfully and precisely repaired, there might not be any long-term effects. Permanent damage, including as mutations, deletions, and amplifications, can happen if the damaged DNA is not quickly repaired or is incorrectly repaired by lower fidelity repair processes. The development, advancement, and unfavourable prognosis of HPV-negative HNSCC are linked to the accumulation of mutations in important tumour suppressor genes (such TP53 and CDKN2A, which encode p53 and p16INK4A, respectively) or signalling pathways (including PI3K–AKT–mTOR and RAS–MAPK pathway genes) (Figure 2) (4).

Symptoms of head and neck cancer can include pain during swallowing and mouth soreness. Depending on where the cancer begins, symptoms may vary. Malignancies that originate in the mouth, throat, sinuses, and salivary glands are classified as head and neck malignancies.

Signs in the throat and mouth:

Head and neck squamous cell carcinoma (HNSCC) is a synonym for the majority of head and neck malignancies, which originate from the mucosal epithelium of the oral cavity, pharynx, and larynx. While pharynx cancers are increasingly linked to HPV, namely HPV-16, oral cavity and larynx cancers are typically connected with tobacco smoking, alcohol addiction, or both. As a result, HNSCC can be classified as HPV-positive or HPV-negative. Even though histological data shows that cellular atypical progresses via different degrees of dysplasia to invasive HNSCC, the majority of individuals with late-stage HNSCC are not diagnosed with a clinically noticeable premalignant lesion (Figure 3) (4).

Head and neck squamous cell carcinoma (HNSCC) originates in the mucosal epithelium lining the oral cavity, pharynx, larynx, and sinonasal tract. According to a model of the ordered histological evolution of HNSCC68, carcinoma in situ develops before invasive carcinoma, and mucosal epithelial cell hyperplasia is followed by dysplasia. It has been discovered that some genomic events are enriched at every stage of development and are listed. In particular, HNSCC formation typically entails turning off tumour suppressor genes, including TP53 and CDKN2A, which encode p16INK4A and p53, respectively) in early stages and PTEN (encoding phosphatase and tensin homologue 14 (PTEN)) in later stages. This is in contrast to most cancers, where oncogenic mutations typically drive tumorigenesis (4).

Protein changes, such as altered or increased expression, can result from genetic and epigenetic modifications. A cancer may develop as a result of the aggregation of these changes in tumour suppressors, proto-oncogenes, and oncogenes. Among the other significant molecules that may be used as therapeutic targets are p53, epidermal growth factor receptor (EGFR), VEGFR, and signal transducer and activator of transcription 3 (STAT3), which are among the critically changed pathways in HNSCC (5).

The most common molecular events that lead to transformation are changes in EGFR and p53, which show up as enhanced migration, angiogenesis, survival, and proliferation as well as a lack of growth control. Over 50% of head and neck cancer cases have mutations in the p53 gene, making it one of the most frequently altered genes in the disease. When the tumour suppressor p53 on chromosome 17q13 is inactivated, cells are unable to respond to stress or damage to their DNA, which results in a lack of growth control. The p53 pathway is frequently dysregulated or altered in addition to p53, which results in additional p53 mutations (5). There are 11 exons in the TP3 gene, the first of which is noncoding. With 393 amino acids, the p53 protein is divided into four regions, each with a distinct function: the C-terminal tetramerisation domain (amino acids 319–360), the N-terminal transactivation domain (amino acids 20–42), the central DNA-binding domain (amino acids 103–292), and the C-terminal regulatory domain (amino acids 364–393). Known as the “guardian of the genome,” wild type p53 is an essential tumour suppressor that keeps the genome stable, preventing the onset of cancer. As a transcription factor, p53 suppresses tumours by controlling the transcription of multiple downstream target genes related to cell cycle arrest, apoptosis, senescence, DNA repair, and metabolism. The primary mechanism by which the p53 protein is kept at a low level in normal, unstressed physiological settings is by degradation by its E3 ubiquitin ligase, MDM2, pirh2, and COP1. Following genotoxic stress exposure, p53 is stabilised and post translationally modified through phosphorylation, acetylation, and other modifications. This leads to a sharp increase in p53 levels, which in turn activates and transcriptionally regulates hundreds of genes involved in cell cycle arrest, senescence, apoptosis, metabolism, and differentiation. When combined, these actions guarantee that damaged DNA does not spread across damaged cells (Figure 4) (6).

A protein known as MDM2, or the murine double minute 2, interacts with p53, lowers its activity, and moves p53 from the nucleus to the cytoplasm. Moreover, MDM2 functions as a ubiquitin ligase. By delivering p53 to the ubiquitin proteasomal system (UPS), this activity of MDM2 aids in the breakdown of functional p53 and reduces the quantity of p53 in the cell. Cell growth stops when genetic damage occurs, and p53 triggers apoptosis, a planned cell death. Due to its capacity to control malignancy, cancer cells have evolved to p53 function in various ways and evade senescence and apoptosis through unique pathways (7). These p53 gene characteristics and mutations aid in the transformation of cancer by allowing cells to avoid cell cycle checkpoints and death. Consequently, the majority of cancer cells depend on p53 mutations to continue existing. This explains the observation of high-frequency p53 mutations in the majority of malignant cell types. All cancer types, however, are known to undergo distinct genomic rearrangements and adaptations in response to unique changes and environmental stimuli. p53 functions and mutations vary depending on the type of cancer, each having its own unique mechanism (7).

It is divided into Invasive and Non- Invasive BC.

Non-Invasive BC Cells: These cells stay within the ducts and do not spread to the breast’s surrounding connective and fatty tissues. The most frequent non-invasive BC kind, accounting for 90% of cases, is ductal carcinoma in situ (DCIS). Less frequently occurring lobular carcinoma in situ (LCIS) is thought to be a sign of an elevated risk of BC.

Invasive BC: BC cells that spread to the surrounding fatty and connective tissues of the breast after breaching the duct and lobular wall. It is possible for cancer to be invasive without also spreading to other organs or lymph nodes (10).

A lump in the breast or underarm is the typical sign of BC. Being familiar with the texture, size, cyclical variations, and skin condition of your breasts can be achieved by performing monthly breast self-examinations (BSEs). BC is generally indicated by symptoms like nine breast swelling or lump (mass), swelling in the armpit (lymph nodes), clear or bloody nipple discharge, nipple pain, inverted (retracted) nipple, scaly or pitted skin on nipple, persistent breast tenderness, and unusual breast pain or discomfort. Underarm lymph nodes are found at the advanced stage (metastatic) of the disease along with other symptoms such unintentional weight loss, shortness of breath from lung metastases, bone pain from bone metastases, and a decrease in appetite from liver metastases (10).

The most frequent cancer in women and a major global cause of death is BC. A diverse collection of tumours, BC has a wide range of prognoses and therapy sensitivity. In order to stratify BC for customised treatment, more biomarkers must be found. DNA topology can be altered by the topoisomerases (TOP) to aid in transcription and replication. Topoisomerase I (TOP1) and Topoisomerase II (TOP2) are the two different forms of TOPs. They are categorised based on their capacity to create temporary single- or double-stranded breaks in DNA. TOPs are important for DNA function and may be targets for cancer treatments. A number of TOP inhibitors are employed in therapeutic settings (11). Enzymes known as DNA TOP are responsible for altering the torsional and flexural strain of DNA molecules. These enzymes have been linked in previous research to a number of eukaryotic and prokaryotic processes, including as chromosome segregation, transcription, recombination, and DNA replication (12).

DNA topology can be altered by the TOP to aid in transcription and replication. TOP1 and TOP2 are the two different forms of TOPs. They are categorised based on their capacity to create temporary single- or double-stranded breaks in DNA. TOPs are important for DNA function and may be targets for cancer treatments. A number of TOP inhibitors are employed in therapeutic settings. One of the many widely acknowledged chemical pathways can inhibit the DNA Topoisomerase enzymes. Substrate competitive inhibition, which is the binding of an inhibitory chemical to the topoisomerase active site to prevent the binding of the DNA substrate, is one possible method. Though recent reports of DNA-competitive inhibitors of other DNA-binding proteins imply that this mechanism may also be viable in DNA TOP, there are no noteworthy instances of topoisomerase-specific inhibitors that function by this manner. The creation of “topoisomerase poisons,” which are made up of ternary protein-DNA-drug complexes that obstruct DNA re-ligation and imprison the enzyme in a “cleavage complex,” is another frequent approach. Because of this compound, the cell’s cytotoxic cleavage complex accumulates to high levels and enzyme turnover is inhibited. The type II TOP are the only ones that exhibit competitive inhibition of the ATP binding site, a third mechanism that stops the enzymatic action powered by ATP hydrolysis. The mechanism of the topoisomerase poisons is of the utmost therapeutic significance. Through the formation of a locked ternary complex of cleaved DNA, protein, and medication that accumulates and has a cytotoxic impact, this method includes stabilising the cleavage complex. The anthracycline medicines were the first known class of topoisomerase inhibitors utilised in cancer treatment. When the anthracyclines were originally isolated from Streptomyces bacteria, it was found that they have both antibacterial and anticancer properties (13).

The Protein Data Bank is the database for the three-dimensional structure data of large biological molecules, such as protein and nucleic acid.

The structure was designed based on literature review using ZINC SKETCH Tool in ZINC20 database (Figure 8).

The canonical smiles of the chemical compound Britanlin E is used in ChemSketch for 3D optimisation (Figure 9).

Canonical Smiles: C=CC)[C@@H]2CC[C@]1(C)C[C@@H] (O)[C@H](O)C(C)=C1C2

Open babel is a format converting tool, which is used to convert the MDL mol format of chemical compound Britanlin E into the pdb format.

The canonical smiles of the chemical compound Britanlin E are given as an input to view the validation of pharmacokinetic (PK) properties.

This is known as PK and pharmacodynamics (PD) analysis. Britanlin E (toxicity) also was modelled effective. Thus, this platform may enable predictions of drug absorption, distribution, metabolism, excretion, and toxicity (ADMET).

The canonical smiles of the chemical compound Britanlin E are used as an input in Molinspiration, and the output includes high quality molecule depiction, molecular database tools supporting substructure and similarity searches, and the calculation of various molecular properties needed in QSAR and drug design.

A crucial tool in computer-assisted drug design and structural molecular biology is molecular docking. Predicting the main binding mode(s) of a ligand with a protein that has a known three-dimensional structure is the aim of ligand-protein docking.

Visualisation in BIOVIA refers to the use of advanced graphical techniques and tools to explore, analyse, and present molecular structures, properties, and interactions within the software suite. It provides researchers with the means to visualise complex biological systems and chemical compounds. The result file is in the format of pdbqt, which is converted into pbq with help of open babel, a format converting tool, the pdb format is joined with the input file which is in pdb. Then finally the pdb format file is visualised in the BIOVIA studio visualisation tool. The molecular interaction, forces involved in it, distance between the molecules are noted.

Its gives a detailed information about the Physiochemical parameters, Lipophilicity, Water solubility, PKs and Drug likeness (Figure 10).

It is a key tool in structural molecular biology and computer-assisted drug design. The goal of ligand-protein docking is to predict the predominant binding mode(s) of a ligand with a protein of known three-dimensional structure.

Visualisation of 3D structure and 2D structure of protein and ligand interaction in BIOVIA discovery tool.