Structural, Quantum Chemical, Molecular Docking, and Dynamics Studies of Quercetin—A Potent Inhibitor for Colon Cancer

According to several studies, phytochemicals, such as polyphenols, flavones, and flavonoids have significant anticancer properties that can combat various malignancies. Even though its action is highly dependent on the intracellular availability of reduced glutathione, Quercetin is regarded as an excellent free-radical scavenging antioxidant flavonoid. Apart from its antioxidant properties, Quercetin has a direct pro-apoptotic action in tumor cells. It has been shown to inhibit the proliferation of multiple human cancer cell lines at various cell cycle stages. The choice of a suitable chemopreventive agent was based on epidemiological studies that showed that consuming a specific dietary component (e.g. Quercetin) can lower the incidence of specific cancer death. MLK4 (KIAA1804) is the second most often altered kinase in colorectal carcinomas with microsatellite stability (MSS) (CRC). MLK4 regulates various physiological cellular processes, including cell cycle, senescence, and apoptosis, and mechanistic evidence suggests MLK4 is involved in carcinogenesis. In this study, the molecular structure of the Quercetin molecule was optimized using DFT/B3LYP method with a cc-pVTZ basis set, and the structural parameters were calculated. The generated vibrational spectra and the optimized molecular geometry were thoroughly reviewed and compared with experimental findings, resulting in a strong correlation. FMOs analysis was performed, which confirms the molecular reactivity of the Quercetin molecule. The anti-tumor efficacy of Quercetin was examined against the colon cancer target protein through in silico parameters, such as molecular docking and dynamics, ADME studies, MM-GBSA calculations, and the Pharmacophore hypothesis. From the analysis, the docked complex showed the highest docking score and maintained the complex stability and flexibility throughout the simulation period. Thus, the present study concluded that Quercetin could be a potent inhibitor of targeted colon cancer protein.