Synthesis, X-ray crystal structure, Hirshfeld surface analysis and computational investigation into the potential inhibitory action of novel 6-(p-tolyl)-2-((p-tolyl)thio)methyl-7H-[1.2.4]triazolo[5,1-b][1,3,4]thiadiazine inhibits the main protease of COVID-19.

In recent times, the novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become a worldwide pandemic. With over 71 million confirmed cases, even though the effectiveness and side effects of the specific drugs and vaccines approved for this disease are still limited. Scientists and researchers from all across the world are working to find a vaccine and a cure for COVID-19 by using large-scale drug discovery and analysis. Heterocyclic compounds are regarded to be valuable sources for the discovery of new antiviral medications against SARS-CoV-2 because virus occurrences are still on the rise, and infectivity and mortality may also rise shortly. In this regard, we have synthesized a new triazolothiadiazine derivative. The structure was characterized by NMR spectra and confirmed by X-ray diffraction analysis. The structural geometry coordinates of the title compound are well reproduced by DFT calculations. NBO and NPA analyses have been performed to determine the interaction energies between bonding and antibonding orbital, and natural atomic charges of heavy atoms. Molecular docking suggests that the compounds may have good affinity for SAR-CoV-2 main protease, RNA-dependent RNA polymerase and nucleocapsid enzymes, particularly the main protease enzyme (binding energy of -11.9 kcal mol-1). The predicted docked pose of the compound is dynamically stable and reports a major van der Waals contribution (-62.00 kcal mol-1) to overall net energy.Communicated by Ramaswamy H. Sarma.

Synthesis, reactions, and biological activities of some new thieno[3,2-c]quinoline and pyrrolo[3,2-c]quinoline derivatives.

2-Bromo-4-fluoroaniline (1) was condensed with ethyl 2-cyano-3-ethoxyacrylate (2) in ethanol to afford 3, which upon refluxing in paraffin oil at 250°C gave 8-bromo-3-cyano-6-fluoroquinoline-4(1H)-one (4). Then, compound 4 was taken as a versatile building block that allows the synthesis of thieno[3,2-c]quinoline, pyrrolo[3,2-c]quinoline, and N-methylpyrrolo[3,2-c]quinoline systems. The newly synthesized compounds and their derivatives were characterized by elemental analysis and spectroscopy (IR, (1)H NMR, (13)C NMR, and mass). Furthermore, some of these synthesized compounds were screened for their biological activities against various pathogenic bacterial and fungal strains. Our results demonstrate that most of the synthesized compounds possess a significant broad antibacterial activity against all strains of both gram-positive and gram-negative bacteria. In addition, compound 5 showed remarkable antifungal activity.