Executive Summary : | Breast cancer, one of the most prevalent cancer in women, is a worldwide severe health concern. Hence, a rapid diagnosis and treatment are crucial for successful outcomes. Although a number of chemotherapeutic options are currently in use, most of them are inappropriate in treating/eradicating cancer cells. Nevertheless, there are quite a few limitations in delivering chemotherapeutic drugs: unprecedented side effects, limited bioavailability, inability to distinguish between cancer and normal cells, inadequate interaction with the target and difficulty in providing a maximum payload of drugs to the intended regions, and so on. As a result, the mortality rate increases leading to the search for an alternative treatment strategy. In this journey, a prodrug is considered a superior alternative for developing a new anticancer medication. For example, self-assembled hybrid prodrugs can be produced by the process of esterification using hydrophobic and hydrophilic drugs, bendamustine, and topotecan, respectively. Upon hydrolysis, the covalent bond between the drugs disrupts, releasing drugs into the desired location and eliminating cancer. In addition, the synergistic activity of bendamustine and topotecan exemplifies its action, causing no side effects to normal cells. The following preliminary work has been carried out at Chemiinformatics and nanodrug delivery lab, Alagappa University, Tamil Nadu, Karaikudi. (i) by using the computation approach, the anticancer prodrug (Bendamustine and Topotecan) was docked with estrogen receptor (ER) protein; (ii) MM/GBSA, and ADME-pharmacokinetics properties were witnessed. The following results were observed (i) an impressive docking score (-9.676 kcal/mol) with four hydrogen bond interactions; (ii) shown to have an excellent binding affinity (∆Gbind -62.542 kcal/mol) and (iii) able to satisfy Lipinski rule of 5 for the drug-likeness property. Given this, the present fills the gap by addressing chemistry, biology, and data science. Based on the preliminary outcome, Molecular Dynamic Simulation, MM/PBSA, Principal Component Analysis (PCA), and DFT will be analyzed. Furthermore, the developed self-assembled hybrid prodrug will be experimented with in animal models (mammalian cell culture, nude mice, etc.) limited to breast cancer. The study's outcome can also be extended to other types of cancer. Moreover, to the best of our knowledge, this is the first report on the development of self-assembled hybrid prodrugs utilizing bendamustine and topotecan targeting breast cancer animal models (in vitro and in vivo). |