DFT, ADMET and Molecular Docking Investigations for the Antimicrobial Activity of 6,6′-Diamino-1,1′,3,3′-tetramethyl-5,5′-(4-chlorobenzylidene)bis[pyrimidine-2,4(1H,3H)-dione]

Abstract

Heterocyclic compounds, including pyrimidine derivatives, exhibit a broad variety of biological and pharmacological activities. In this paper, a previously synthesized novel pyrimidine molecule is proposed, and its pharmaceutical properties are investigated. Computational techniques such as the density functional theory, ADMET evaluation, and molecular docking were applied to elucidate the chemical nature, drug likeness and antibacterial function of molecule. The viewpoint of quantum chemical computations revealed that the molecule was relatively stable and has a high electrophilic nature. The contour maps of HOMO-LUMO and molecular electrostatic potential were analyzed to illustrate the charge density distributions that could be associated with the biological activity. Natural bond orbital (NBO) analysis revealed details about the interaction between donor and acceptor within the bond. Drug likeness and ADMET analysis showed that the molecule possesses the agents of safety and the effective combination therapy as pharmaceutical drug. The antimicrobial activity was investigated using molecular docking. The investigated molecule demonstrated a high affinity for binding within the active sites of antibacterial and antimalarial proteins. The high affinity of the antibacterial protein was proved by its low binding energy (−7.97 kcal/mol) and a low inhibition constant value (1.43 µM). The formation of four conventional hydrogen bonds in ligand–protein interactions confirmed the high stability of the resulting complexes. When compared to known standard drugs, the studied molecule displayed a remarkable antimalarial activity, as indicated by higher binding affinity (B.E. −5.86 kcal/mol & Ki = 50.23 M). The pre-selected molecule could be presented as a promising drug candidate for the development of novel antimicrobial agents.

Phytochemical Discrimination, Biological Activity and Molecular Docking of Water-Soluble Inhibitors from Saussurea costus Herb against Main Protease of SARS-CoV-2

“…Therefore, for infectious diseases in particular, people need to go back to medicinal plants, which are a huge and all-natural drug store [ 36 ]. This study put a special emphasis on finding inhibitors against the main protease (M pro ), as it is considered an ideal target for the treatment of COVID-19 [ 37 , 38 , 39 , 40 , 41 , 42 ]. The blind molecular docking approach was performed utilizing the elucidated compounds extracted in water at room temperature from Saussurea costus .…”

Acridone Alkaloids: In-Silico Investigation Against SARS-CoV-2 Main Protease

“…Interestingly, none of the compounds is a substrate for P-gp (Permeability glycoprotein). P-gp is an efflux transporter pump found in the cell membrane which is responsible for conveying drugs away from the cell membrane and cytoplasm which causes therapeutic failure when the concentration of the drug is reduced [ 38 ].…”

“…Ionization energy is defined as the energy required to remove an electron from a molecule’s ground state and it is related to E HOMO . Hence the higher the E HOMO of a molecule, the lower its potential to donate an electron and high value indicates chemical stability [ 38 ]. E LUMO is related to the electron affinity which is defined as the energy released when a molecule in the ground state captures an electron and the lower the E LUMO of a molecule, the more its ability to accept electrons from nearby molecules.…”

One‐Pot Microwave‐Assisted Synthesis, in Vitro Anti‐inflammatory Evaluation and Computer‐Aided Molecular Design of Novel Sulfamide‐Containing Bisphosphonates Derivatives

“…Computational techniques such as the density functional theory (DFT), ADMET evaluation, and molecular docking were performed to the previously synthesized molecules 4 a, 4 b, 4 c and 4 d for explaining the reactivity and selectivity of various types of organic reaction, [66] and to elucidate the chemical nature, drug likeness and anti‐inflammatory activity of molecules, [67] also predicts drug‐receptor interactions that hold a protein and a ligand together in a bound state [68]…”