Screening of Potential Breast Cancer Inhibitors through Molecular Docking and Molecular Dynamics Simulation
Sangavi Pandi1, Langeswaran Kulanthaivel1, Gowtham Kumar Subbaraj2
1Cancer Genetics & Molecular Biology Laboratory, Department of Bioinformatics, Science Campus, Alagappa University, Karaikudi, Tamil Nadu, India.
Abstract:
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.
Insights
Virtual screening identified novel compounds that inhibit Cyclooxygenase-2 (COX-2), offering potential new treatments for breast cancer. These inhibitors show promising interactions with the COX-2 enzyme, paving the way for therapeutic strategies.
Area of Science:
- Biochemistry
- Computational Chemistry
- Oncology
Background:
- Cyclooxygenase-2 (COX-2) is frequently overexpressed in human cancers, including breast cancer, making it a target for therapeutic intervention.
- Identifying selective COX-2 inhibitors is crucial for developing new prognostic and therapeutic strategies for breast cancer treatment.
Purpose of the Study:
- To identify potential Cyclooxygenase-2 (COX-2) inhibitors through virtual screening of chemical databases.
- To evaluate the drug-likeness and binding mechanisms of identified compounds with COX-2 for breast cancer therapy.
Main Methods:
- Virtual screening of Maybridge, NCI, and Enamine databases based on structural similarity to known COX-2 inhibitors.
- Filtering compounds using Lipinski's rule of five and assessing Absorption, Distribution, Metabolism, and Excretion (ADME) properties.
- Performing molecular docking and simulations to analyze the interaction mechanism between hit compounds and the COX-2 binding site.
Main Results:
- Several compounds exhibited favorable drug-likeness and ADME properties.
- Molecular docking revealed that hydrophobic interactions and hydrogen bonds are key forces in the binding of identified compounds to COX-2.
- Specific compounds (Maybridge_55417, NCI_30552, Enamine_62410) showed significant affinity for COX-2.
Conclusions:
- The identified in silico compounds demonstrate potential as therapeutic agents targeting COX-2 in breast cancer.
- These compounds may inhibit COX-2 activity, potentially reducing the incidence and progression of breast cancer.
- The study highlights the efficacy of virtual screening and molecular docking in discovering novel drug candidates for cancer therapy.
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