Screening of Potential Breast Cancer Inhibitors through Molecular Docking and Molecular Dynamics Simulation

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.

Drug repositioning to discover novel ornithine decarboxylase inhibitors against visceral leishmaniasis

“…Consequently, the global descriptors were enumerated for ceftaroline fosamil and rimegepant, including ionization potential (4.29 and 6.01 eV), electron affinity (3.79 and 0.92 eV), electronegativity (4.04 and 3.46 eV), chemical potential (−4.04 and −3.46 eV), hardness (0.25 and 2.54 eV), softness (4.00 and 0.39 eV), and electrophilicity (32.64, and 2.351 eV) respectively. On the other hand, the global descriptors were also evaluated, including ionization potential (−5.77 eV), electron affinity (−0.64 eV), electronegativity (3.20 eV), chemical potential (−3.20 eV), hardness (3.13 eV), softness (0.31 eV), and electrophilicity (1.63 eV) for pentamidine 54 …”

“…The density functional theory was performed for the top two screened compounds to measure their chemical reactivity. The frontier 54 Additionally, the molecular electrostatic potential surface explores the charge distribution and predicts the electrophile (blue color) and nucleophile (red color) regions of compounds (Figure 4). So, using the DFT/B3LYP-D method at the 6-31*G basis set, the molecular electrostatic potential surface for ceftaroline fosamil, rimegepant, and pentamidine was calculated to be À88.77 to +75.79 kcal/mol, À47.85 to +43.27 kcal/mol, and À 50.17 to +43.01 kcal/mol, respectively (Table 3).…”

Natural compound targeting BDNF V66M variant: insights from in silico docking and molecular analysis

“…In silico analysis, according to Lipinski's criterion, the chemical structures of the selected compounds showed useful drug-like properties that increased oral bioavailability (Chandran et al 2022 ; Pandi et al 2022 ). Oral bioavailability is related to the active form of a medicinal compound that makes it unmodified for systemic circulation.…”

Multi-Target Effect of Aloeresin-A against Bacterial and Host Inflammatory Targets Benefits Contact Lens-Related Keratitis: A Multi-Omics and Quantum Chemical Investigation

“…The target bacterial and host protein structures were prepared by adding hydrogen atoms, refining bond orders, creating disulfide bonds, deleting water molecules, and optimizing missing atoms using the PROPKA function of Protein Preparation Wizard, Maestro-Schrödinger version 11.2 [42]. The Glide module of Maestro-Schrödinger version 11.2 [43] was employed to perform molecular docking between phytochemicals against bacterial and host target proteins. Blind docking was executed to discover the likelihood of phytochemicals interacting with any region of the target proteins.…”