ABSTRACT
Due to theirinteresting hydrogen-bonding properties, Schiff bases are known for their variety of applications in chemistry and medicinal chemistry. In this work, the interaction between symmetrical Schiff base ligand (L: bis [4-hydroxy-6-methyl-3-{(1E)-N-[2 (ethylamino) ethyl] ethanimidoyl}-2H-pyran-2-one]) and cancer cells, neurological, viruses and bacteria receptors was studied theoretically. Density functional theory (DFT) was used to determine the geometry, reactivity and electronic properties of this ligand. Homology modeling and molecular docking were performed to check their biological and medicinal properties, including anticancer, antiviral, antibacterial and neurological activities. DFT revealed that the mulliken charges, the molecular orbitals (HOMO and LUMO) and MEP results are in a good agreement to the localization of electrophilic and nucleophilic attack sites. The theoretical study showed a high chemical reactivity and a low kinetic stability of the ligand. The docking study results revealed that the ligand exhibits a good biological activity against leukemia, breast cancer, Alzheimer and Covid-19 with binding energy values of -7.36 kcal/mol, -6.35 kcal/mol, -6.19 kcal/mol and -5.58 kcal/mol, respectively. These results are explained by the low values of binding energy and inhibition constant and multiple H-bonds.
ABSTRACT
The crystals of new ligand, namely (3E)-6-methyl-3-{1-[(pyridin-3-ylmethyl) amino] ethylene}-2H-pyran-2, 4(3H)-dione) (LAT1), were synthesized using the evaporation solution technique. Single-crystal X-ray diffraction and physico-chemical characterization (ATR, proton and carbon-13 NMR and UV-Visible) of LAT1 were reported. In addition, Hirshfeld surface analysis (HSA) of the solid compound, structure optimization, Mulliken and NBO charges, global indices of reactivity, local reactivity descriptors and molecular electrostatic potential (MEP) of the ligand were investigated theoretically. XRD analysis showed that LAT1 crystallizes in the triclinic space group P-1 and the structure was stabilized through hydrogen bonds. HAS revealed that H…H (46.5%) and O…H (25.7%) contacts are in control of crystal stacking. The energy gap (4.679 eV) and reactivity descriptors indicate the stability of LAT1. The Mulliken and NBO charges showed that the protons have a positive charge and the heteroatoms exhibit negative charges. The Fukui function and MEP study revealed that the heteroatoms are the most reactive sites for an electophilic attack on the ligand. Molecular docking simulation shows that the significant binding affinity of LAT1 with SARS-CoV-2/Mpro is due to the formation of high number of hydrogen bonds.
ABSTRACT
Currently, Covid-19 pandemic infects staggering number of people around the globe and causes a high rate of mortality. In order to fight this disease, a new coumarin derivative ligand (4-[(pyridin-3-ylmethyl) amino]-2H-chromen-2-one) (LTA) has been synthesized and characterized by single-crystal X-ray diffraction, NMR, ATR, UV-Visible and cyclic voltammetry. Chemical reactivity, kinetic and thermodynamic studies were investigated using DFT method. The possible binding mode between LTA and Main protease (Mpro) of SARS-CoV-2 and their reactivity were studied using molecular docking simulation. Single crystal X-ray diffraction showed that LTA crystallizes in a monoclinic system with P2 1 space group. The reactivity descriptors such as nucleophilic index confirm that LTA is more nucleophile, inducing complexation with binding species like biomolecules. The kinetic and thermodynamic parameters showed that the mechanism of crystal formation is moderately exothermic. The binding energy of the SARS-CoV-2/Mpro-LTA complex and the calculated inhibition constant using docking simulation showed that the active LTA molecule has the ability to inhibit SARS-CoV-2.