Cyclooxygenase-2 (COX-2) is a key enzyme involved in overexpression in several human cancerous diseases including breast cancer. By performing efficient virtual screening in a series of active molecules or compounds from the Maybridge, NCI (National Cancer Institute), and Enamine databases, potential identification of COX-2 inhibitors could lead to new prognostic strategies in the treatment of breast cancer. Based on a 50% structural similitude, compounds were chosen as the inductive model of COX-2 inhibitions from these databases. Selected compounds were filtered and tested with Lipinski’s rule of five followed by absorption, distribution, metabolism, and excretion (ADME) properties. Subsequently, molecular docking was performed to achieve accuracy in screening and also to find an interactive mechanism between hit compounds with their respective binding sites. Simultaneously, molecular simulations of top-scored compounds were selected and coded such as Maybridge_55417, NCI_30552, and Enamine_62410. Chosen compounds were analyzed and interpreted with COX-2 affinity. Results endorsed that hydrophobic affinity and optimum hydrogen bonds were the forces driven in the interactive mechanism of in silico hits compounds with COX-2 and can be used as efficient alternative therapeutic agents targeting deleterious breast cancer. With these in silico findings, compounds identified may prevent the action of the COX-2 enzyme and thereby diminish the incidence of breast cancer.
Introduction: Non-Small Cell Lung Cancer is the most prevalent type of cancer in lung cancer. Chemotherapy, radiation therapy, and other conventional cancer treatments have a low success rate. Thus, creating new medications is essential to halt the spread of lung cancer.Methods: In this study bioactive nature of lochnericine against Non-Small Cell Lung Cancer (NSCLC) was analyzed using various computational approaches such as quantum chemical calculations, molecular docking, and molecular dynamic simulation. Furthermore, the MTT assay shows the anti-proliferation activity of lochnericine.Results and Discussion: Using Frontier Molecular Orbital (FMO), the calculated band gap energy value associated with bioactive compounds and the molecule’s potential bioactivity is confirmed. The H38 hydrogen atom and O1 oxygen atom in the molecule are effectively electrophilic, and potential nucleophilic attack sites were confirmed through analysis of the Molecular electrostatic potential surface. Furthermore, the electrons within the molecule were delocalized, which confers bioactivity on the title molecule and was authorized through Mulliken atomic charge distribution analysis. A molecular docking study revealed that lochnericine inhibits non-small cell lung cancer-associated targeted protein. The lead molecule and targeted protein complex were stable during molecular dynamics simulation studies till the simulation period. Further, lochnericine demonstrated remarkable anti-proliferative and apoptotic features against A549 lung cancer cells. The current investigation powerfully suggests that lochnericine is a potential candidate for lung cancer.
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