Development of new bioactive molecules to treat breast and lung cancer with natural myricetin and its derivatives: A computational and SAR approach

Abstract

Each biopharmaceutical research and new drug development investigation is targeted at discovering novel and potent medications for managing specific ailments. Thus, to discover and develop new potent medications, it should be performed sequentially or step by step. This is because drug development is a lengthy and risky work that requires significant money, resources, and labor. Breast and lung cancer contributes to the death of millions of people throughout the world each year, according to the report of the World Health Organization, and has been a public threat worldwide, although the global medical sector is developed and updated day by day. However, no proper treatment has been found until now. Therefore, this research has been conducted to find a new bioactive molecule to treat breast and lung cancer—such as natural myricetin and its derivatives—by using the latest and most authentic computer-aided drug-design approaches. At the beginning of this study, the biological pass prediction spectrum was calculated to select the target protein. It is noted that the probability of active (Pa) score is better in the antineoplastic (Pa: 0.788–0.938) in comparison with antiviral (Pa: 0.236–0.343), antibacterial (Pa: 0.274–0.421), and antifungal (Pa: 0.226–0.508). Thus, cancerous proteins, such as in breast and lung cancer, were picked up, and the computational investigation was continued. Furthermore, the docking score was found to be -7.3 to -10.4 kcal/mol for breast cancer (standard epirubicin hydrochloride, -8.3 kcal/mol), whereas for lung cancer, the score was -8.2 to -9.6 kcal/mol (standard carboplatin, -5.5 kcal/mol). The docking score is the primary concern, revealing that myricetin derivatives have better docking scores than standard chemotherapeutic agents epirubicin hydrochloride and carboplatin. Finally, drug-likeness, ADME, and toxicity prediction were fulfilled in this investigation, and it is noted that all the derivatives were highly soluble in a water medium, whereas they were totally free from AMES toxicity, hepatotoxicity, and skin sensitization, excluding only ligands 1 and 7. Thus, we proposed that the natural myricetin derivatives could be a better inhibitor for treating breast and lung cancer.

In silico design of novel bioactive molecules to treat breast cancer with chlorogenic acid derivatives: a computational and SAR approach

“…Asp351, Ser530, and Phe404 are the common amino acid residues of PDB ID 7KCD that form maximum hydrogen bonds with ligands. The findings of Akash et al (2022) support interactions of this kind and the participation of specific amino acids in binding.…”

“…The online tool PASS was used to predict the antiviral, antibacterial, antifungal, and antineoplastic effectiveness of derivatives, as developed by SAR studies ( Akash et al, 2022 ). The following acquisition PASS values were obtained: Pa score 0.383–0.479 for antiviral, 0.222–0.505 for antibacterial, 0.428–0.638 for antifungal, and 0.469–0.802 for antineoplastic.…”

Anti-viral drug discovery against monkeypox and smallpox infection by natural curcumin derivatives: A Computational drug design approach

“…The docking studies modeling was executed to investigate the molecular interaction strategy and acquire documentation on the binding capacity and ligand effectiveness to inhibit the targeted protein. In the current study, the molecular docking analysis was evaluated with the cooperation of the PyRx AutoDock tools application, version 4.2 ( Akash et al., 2022a ; Rizvi et al., 2013 ). The automatic maximized function was used to compose the 3D grid for ligand-receptor interaction during molecular docking.…”

Inhibitory Effect and Mechanism of Ursolic Acid on Cisplatin‐Induced Resistance and Stemness in Human Lung Cancer A549 Cells

“…It has been reported that UA has the ability to modulate a variety of signaling pathways associated with cancer survival and progression [91,92]. For example, UA reduced the expression of Stat3 and its downstream targets to inhibit the proliferation of prostate cancer and hepatocellular carcinoma [88,[93][94][95]. Results also showed that UA suppressed myeloma growth through Stat3-mediated inhibition [51].…”