ABSTRACT
The viral RNA-dependent RNA polymerase (RdRp) complex is used by SARS-CoV-2 for genome replication and transcription, making RdRp an interesting target for developing the antiviral treatment. Hence the current work is concerned with the green synthesis, characterization and docking study with the RdRp enzyme of the series of novel and diverse hydrazones and pyrazoles. 4-Methyl-2-(2-(1-phenylethylidene)hydrazineyl)thiazole-5-carbohydrazide was prepared and then condensed with different carbonyl compounds (aldehydes and ketones either carbocyclic aromatic or heterocyclic) afforded the corresponding hydrazide-hydrazones. The combination of the acid hydrazide with bifunctional reagents such as acetylacetone, ß-ketoesters (ethyl acetoacetate and ethyl benzoylacetate) resulted in the formation of pyrazole derivatives. The synthesized compounds were all obtained through grinding method using drops of AcOH. Various analytical and spectral analyses were used to determine the structures of the prepared compounds. Molecular Operating Environment (MOE®) version 2014.09 was used to estimate interactions between the prepared thiazole/hydrazone hybrids and RdRp obtained from the protein data bank (PDB: 7bv2) using enzyme-ligand docking for all synthesized derivatives and Remdesivir as a reference. Docking results with the RdRp enzyme revealed that the majority of the investigated drugs bind well to the enzyme via various types of interactions in comparison with the reference drug.
ABSTRACT
Substituted thiosemicarbazones derived by 2-quinolone were synthesized to investigate their complexation capability towards Cu(I), Cu(II) and Ni(II) salts. The structure of the complexes was established by ESI, IR and NMR spectra in addition to elemental analyses. Monodetate Cu(I) quinoloyl-substituted ligands were observed, whereas Ni(II) and Cu(II) formed bidentate-thiosemicarbazone derived by 2-quinolones. Subsequently, molecular docking was used to evaluate each analog's binding affinity as well as the inhibition constant (ki) to RdRp complex of SARS-CoV-2. Docking results supported the ability of the tested complexes that potentially inhibit the RdRp of SARSCov-2 show binding energy higher than their corresponding ligands. Additionally, ADMET prediction revealed that some compounds stratify to Lipinski's rule, indicating a good oral absorption, high bioavailability good permeability, and transport via biological membranes. Therefore, these metals-based complexes are suggested to be potentially good candidates as anti-covid agents.
ABSTRACT
We report herein a new series of synthesized N-substituted-2-quinolonylacetohydrazides aiming to evaluate their activity towards SARS-CoV-2. The structures of the obtained products were fully confirmed by NMR, mass, IR spectra and elemental analysis as well. Molecular docking calculations showed that most of the tested compounds possessed good binding affinity to the SARS-CoV-2 main protease (Mpro) comparable toRemdesivir.
ABSTRACT
During formylation of 2-quinolones by DMF/Et3N mixture, the unexpected 3,3'-methylenebis(4-hydroxyquinolin-2(1H)-ones) were formed. The discussed mechanism was proved as due to the formation of 4-formyl-2-quinolone as intermediate. Reaction of the latter compound with the parent quinolone under the same reaction condition gave also the same product. The structure of the obtained products was elucidated via NMR, IR and mass spectra. X-ray structure analysis proved the anti-form of the obtained compounds, which were stabilized by the formation hydrogen bond. Molecular docking calculations showed that most of the synthesized compounds possessed good binding affinity to the SARS-CoV-2 main protease (Mpro) in comparable to Darunavir.