Exploring Schiff base ligand inhibitor for cancer and neurological cells, viruses and bacteria receptors by homology modeling and molecular docking

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.

Crystal structure, chemical reactivity, kinetic and thermodynamic studies of new ligand derived from 4-hydroxycoumarin: Interaction with SARS-CoV-2.

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.