Rational Approach toward COVID-19's Main Protease Inhibitors: A Hierarchical Biochemoinformatics Analysis.

This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 Mpro through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. In silico molecular docking simulations revealed promising ligands with favorable binding affinities for Mpro, ranging from -6.2 to -9.5 kcal/mol. Moreover, molecular dynamics simulations demonstrated the stability of protein-ligand complexes over 200 ns, maintaining protein secondary structures. MM-PBSA analysis revealed favorable interactions between ligands and Mpro, with negative binding energy values. Hydrogen bond formation capacity during molecular dynamics was confirmed, indicating consistent interactions with Mpro catalytic residues. Based on these findings, selected ligands show promise for future studies in developing COVID-19 treatments.

Antioxidant capacity of simplified oxygen heterocycles and proposed derivatives by theoretical calculations.

CONTEXT: Some structural properties can be involved in the antioxidant capacity of several polyphenol derivatives, among them their simplified structures. This study examines the contribution of simplified structure for the antioxidant capacity of some natural and synthetic antioxidants. The resonance structures were related to the π-type electron system of carbon-carbon double bonds between both phenyl rings. Trans-resveratrol, phenyl-benzofuran, phenyl-indenone, and benzylidene-benzofuranone are the best basic antioxidant templates among the simplified derivatives studied here. Additionally, the stilbene moiety was found on the molecules with the best antioxidant capacity. Furthermore, our investigation suggests that these compounds can be used as antioxidant scaffold for designing and developing of new promising derivatives. METHODS: To investigate the structure-antioxidant capacity for sixteen simplified natural and proposed derivatives we have employed density functional theory and used Gaussian 09. Our DFT calculations were performed using the B3LYP functional and the 6-31+G(d,p) basis set. All electron transfer mechanisms were investigated by using values of HOMO, ionization potential, energy affinity, stabilization energies, and spin density distributions.

Essential features for antioxidant capacity of ascorbic acid (vitamin C).

Vitamin C or ascorbic acid is an indispensable micronutrient for human health found principally on citrus species such as lemon and orange fruits and vegetables. It was involved in the production of proteins such as collagen. Its biochemical mechanism is related to its antioxidant capacity; however, its function at the cellular level is still unclear. Several theoretical studies about antioxidant and redox mechanisms for ascorbic acid were suggested; however, no derivative was proposed. Thereby, an electronic study of antioxidant capacity for ascorbic acid derivatives was performed using theoretical chemistry at the DFT/ B3LYP/6-311 + + (2d,2p) level of theory. Simplified derivatives show that enol hydroxyls are more important than any other functional group. The vicinal enolic hydroxyl on ß position is more important for antioxidant capacity of ascorbic than hydroxyl on α position. According to our molecular modifications, the keto-alkene compound showed the best values when compared to ascorbic acid in some molecular characteristics. No lactone derivatives have superior application potential as antioxidant when compared with ascorbic acid. Several structures are possible to be proposed and were related to spin density contributions and the increase of chemical stability. New promising structural derivatives related to ascorbic acid can be developed in the future.

Molecular modification approach on kojic acid derivatives as antioxidants related to ascorbic acid.

A hypothetical study by using molecular modeling for antioxidant capacity of kojic acid derivatives was performed using quantum chemistry calculations by DFT/B3LYP/6-311++G(3d,2p). Four modification approaches were considered namely simplification, functional modifications, ring regioisomerism, and hydroxylation. Molecular orbitals, single-electron transfers, hydrogen atom transfers, and spin density distributions were used for antioxidant prediction. In accordance with HOMO, LUMO, Gap, ionization potential, bond dissociation energy, and stabilization energy, the molecular simplifications of kojic acid show that enol moiety is more important for antioxidant capacity than alcohol group. Few molecular modifications on alcohol or enol position were more potent than kojic acid. The π conjugation system among ether, alkene, and hydroxyl moieties can be involved on resonance effects of better compounds. A different performance was observed on alcohol molecular modifications when compared to enol position. All lactone derivatives were more potent than kojic acid on both mechanisms, and their hydroxylated derivatives were more potent than ascorbic acid. In conclusion, the ring regioisomers and its hydroxylated derivatives have better antioxidant capacity than kojic acid. Graphical Abstract The theoretical study using molecular modeling for antioxidant capacity prediction of kojic acid was more related to enol moiety than alcohol. The regioisomerism and hybrid derivatives show that the lactone derivatives increase antioxidant capacity more than the pyrone derivatives.