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Top1. Introduction
Over the past few decades, the world has been suffering from a persistent disease called cancer. A leading cause of death, cancer, is prevalent all over the world without any discrepancies in the economic status of the country. According to the statistics of 2012, speculatively 1.7 million people were diagnosed and near about half a million people died of the disease. This data is expected to attain an increment worldwide due to the consistent growth of the population particularly in underdeveloped countries (Bray et al., 2018; Eggersmann et al., 2019). According to the estimation of WHO in 2020, 685 000 deaths occurred globally and there were 2.3 million women diagnosed with breast cancer (Bray et al., 2018). The etiology of this disease is based on the features like the position of the ovary, the variation in age-specific risks, and being the child-bearer (Alam & Khan, 2017; MacMahon, 2006). Lobular and ductal/lobular carcinoma cases were more likely to be diagnosed with stage III/IV, measuring ⩾5.0 cm in women aged 50–89 years. Depending upon the site, breast cancer is of two types namely non-invasive and invasive (Li et al., 2005; McDonald et al., 2016).
A syndicate of networks has led to the establishment of prominent pathways for breast cancer. There are four members of the ErbB family- ErbB1, ErbB2, ErbB3 and ErbB4. These are cell surface receptors with involvement in growth signaling, survival, and cell proliferation. The association of ErbB2 with other types of ErbBs receptors enhances the signaling intensity and dimer stability as it is the preferred dimerization partner (Arteaga & Engelman, 2014; Asp et al., 2016). Researchers suggest that amplification of ErbB2 is observed in 30 percent of the patients, and often leads to cancer development and cellular transformation. The interaction between nucleolin and ErbB2 enhances the Invitro cellular transformation and increases the risk of mortality along with the disease progression (Wolfson et al., 2018).
Pyrimidine, a privileged scaffold, plays a vital role in various biological processes like cancer pathogenesis owing to its resemblance in structure with the nucleotide base pair of DNA and RNA. The further derivation of this moiety has led to the development of dihydropyrimidininone (DHPMs) which are also prominent as potent anticancer agents. Therefore, several studies have been conducted regarding further potentiating these moieties as significant breast cancer antagonists (Mahapatra et al., 2021; Matos et al., 2018).
The evolution of computer-aided drug designing, and numeric computer modeling has given us the scope of designing the molecules and analyzing them for the required activities in a quickly accurate manner. The QSAR approach allows us to discover the mathematical correlation between the structure of the drug and its biological activity. The molecular docking analysis is significant in determining the mechanism of interaction between the said molecules and the active site of the receptor and provides the results in the form of binding affinity (Das et al., 2021). A 3-D QSAR study was conducted on substituted benzimidazole derivatives linked oxadiazoles as potential inhibitors of EGFR and ErbB2 receptor (Akhtar et al., 2017). Previously, in 2016, 3D QSAR studies of novel dioxin containing pyrazoline derivatives with thiourea were reported for the HER2 receptor (Vickers, 2017). There has been no report of QSAR model based on the dihydropyrimidinones as ErbB2 antagonists.