A new Thiadiazole-triazine derivative: Structural investigation, DFT studies, ADME-T analysis and SARS-CoV-2 activity by docking simulation

Abstract

The present work involves the synthesis of thiadiazole-triazine derivative 7-[2-(4-bromophenyl)ethenyl]-3‑tert‑butyl‑4H-[1,3,4]thiadiazolo[2,3-c][1,2,4]triazin-4-one (TCA3) and spectroscopic characterization is done using NMR and X-ray diffraction techniques. The single crystal X-ray diffraction study unravels the 3D structure of the compound TCA3. The compound crystallizes in the monoclinic crystal system with the space group P21/c. The crystal structure analysis revealed that various CH…O, CH…N, and CH…Br interactions are responsible for crystal packing. Furthermore, Hirshfeld surface analysis has been performed to visualize and analyze the intermolecular interactions observed in the crystal structure. Energy framework analysis was used to explore the molecular architecture in the crystal, and to calculate the molecular interaction energies of the compound TCA3. DFT calculations have also been carried out to explore the various physicochemical properties of the compound like HOMO-LUMO energy gap of the molecule, reactive sites present in the molecule using MEP analysis. The energy gap of the molecule is found to be 4.592 eV. Also, to know the strength and nature of intramolecular interaction energy using RDG analysis. Finally, the potential inhibitory activity of the titled compounds and their drug-likeness are demonstrated by ADME-T calculations. Further, The structure-activity relationships established through molecular docking studies showed that the compound TCA3 strongly binds to the receptors Mpro (-8.2 Kcal/mol) which confirm its inhibition activity against COVID-19.