Abstract
Schiff bases encompassing a 1,2,3-triazole motif were synthesized using an efficient multi-step synthesis. The formations of targeted Schiff base ligands were confirmed by different spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, and CHN analysis). The spectral data analysis revealed that the newly designed hydrazones exist as a mixture of trans-E and cis-E diastereomers. Densityfunctional theory calculations (DFT) for the Schiff bases showed that the trans-trans form has the lowest energy structure with maximum stability compared to the other possible geometrical isomers that could be present due to the orientation of the amidic NH–C=O group. The energy differences between the trans-trans on one side and syn-syn and syn-trans isomers on the other side were 9.26 and 5.56 kcal/mol, respectively. A quantitative structure-activity relationship investigation was also performed in terms of density functional theory. The binding affinities of the newly synthesized bases are, maybe, attributed to the presence of hydrogen bonds together with many hydrophobic interactions between the ligands and the active amino acid residue of the receptor. The superposition of the inhibitor N3 and an example ligand into the binding pocket of 7BQY is also presented. Further interesting comparative docking analyses were performed. Quantitative structure-activity relationship calculations are presented, illustrating possible inhibitory activity. Further computer-aided cytotoxicity analysis by Drug2Way and PASS online software was carried out for Schiff base ligands against various cancer cell lines. Overall, the results of this study suggest that these Schiff base derivatives may be considered for further investigation as possible therapeutic agents for COVID-19.
Highlights
In order to investigate the stability of the expected geometrical isomers, the optimized molecular structures were predicted by Densityfunctional theory calculations (DFT) calculations at the B3LYP 6‒311G (d,p) basis set
As we have previously reported, the electronic nature of the attached substituent to the arylidene part plays a significant role in stabilizing one geometrical isomer over the the arylidene part plays a significant role in stabilizing one geometrical isomer over the others where such groups’ polar nature could affect the strength of the intramolecular others where such groups’ polar nature could affect the strength of the intramolecular HH-bonding
The spectroscopic data of the synthesized compounds showed the presence of E/Z geometrical isomers and the cis/trans conformers
Summary
After the discovery of Schiff bases [7], millions of chemical structural variations were investigated They were designed and developed to obtain the best chemotherapeutic results, especially for SBs incorporating a heterocyclic ring [8,9,10]. Among the significant class of nitrogen heterocyclic motifs, 1,2,3addition, among the significant class of nitrogen heterocyclic motifs, 1,2,3-triazoles have triazoles haveof been the topicinterest of substantial interest due to their of broad spectrum of pharbeen the topic substantial due to their broad spectrum pharmacological uses macological uses and flexibility to modify their scaffolds for a particular biological appliand flexibility to modify their scaffolds for a particular biological application [16]. SB linkages [25,26,27,28]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
