Synthesis, DFT, in-silico molecular docking, molecular dynamic simulation and ADMET studies of (Z)-2,6-bis(4-bromophenyl)-3,3-dimethyl-4-(2-(2,4,6-trichlorophenyl) hydrazono) piperidine derivatives against the SARS-CoV-2 main-protease
- Authors
- Type
- Published Article
- Journal
- Zeitschrift für Physikalische Chemie
- Publisher
- De Gruyter
- Publication Date
- Mar 05, 2024
- Volume
- 238
- Issue
- 4
- Pages
- 729–762
- Identifiers
- DOI: 10.1515/zpch-2023-0397
- Source
- De Gruyter
- Keywords
- License
- Yellow
Abstract
Nowadays, over 200 countries face a wellbeing emergency because of epidemiological disease COVID-19 caused by the SARS-CoV-2 virus. It will cause a very high effect on the world economy and the worldwide health sector. The present work is an investigation of the newly synthesized (Z)-2,6-bis(4-bromophenyl)-3,3-dimethyl-4-(2-(2,4,6-trichlorophenyl) hydrazono) piperidine (BBDTHP) molecule inhibitory potential against important protein targets of SARS-CoV-2 using computational approaches. For the title compound BBDTHP, spectroscopic characterization like FT-IR, 1H-NMR, 13C-NMR, 1H–1H COSY and 1H–13C COSY spectrum were carried out. The geometry of the compound had been optimized by the DFT method and its results were compared with the X-ray diffraction data. The calculated energies for the Highest occupied molecular orbital (HOMO) and the Lowest unoccupied molecular orbital (LUMO) showed the stability and reactivity of the title compound. The molecular electrostatic potential (MEP) picture was drawn using the same level of theory to visualize the chemical reactivity and charge distribution on the molecule. Molecular docking study performed for the synthesized compound revealed an efficient interaction with the COVID-19 protease and resulted in good activities. We hope the present study would help workers in the field to develop potential vaccines and therapeutics against the novel coronavirus. Virtual ADME studies were carried out as well and a relationship between biological, electronic and physicochemical qualifications of the target compound was determined. Toxicity prediction by computational technique for the title compound was also carried out. From the molecular dynamic simulations study, we confirmed hydrogen bonding interactions and stability of the molecule.
