## 2 Results and Discussion
### Molecular Docking Studies  
In order to provide a comprehensive rationale for the obtained biological activities, we docked the most active compounds,**5a** and **5i**, into glucosamine 6-phosphate synthase (GlcN6P) and methionyl-trna-synthease (1 PFV). GlcN6P catalyzes a multifarious reaction comprising both sugar isomerization (fractosamine-6-phosphate to glucosamine-6-phosphate) and ammonia transfer (\(L\)-glutamine to Fru-6-P) [48; 49; 50]. This reaction initiates a pathway that finally drives the production of uridine 5\({}^{\prime}\)-diphospho-\(N\)-acetyl-\(d\)-glucosamine. This nucleotide sugar is used to assemble the macromolecules essential for constructing cell walls, such as the macromolecules with several amino sugar units, like chitin or proteins in fungi, and lipopolysaccharidesaccharides and peptide glycan in bacteria. GlcN6P synthase inhibition is fatal, even for a short time, in prokaryotic cells but not in human cells. Therefore, it is considered as a promising target for developing antibacterial and antifungal agents. The compounds, except **5a** enantiomer (which has the most potent antibacterial activity among all the synthesized compounds), exhibit interactions with several amino acid residues at the active site of GlcN6P and reveal low binding energy. They also share several amino acids with the positive controls, Ampicillin and Tetracycline (Table 7) and (Figure 8). Infections caused by antibiotic-resistant pathogens have raised markedly in recent years. Over 60% of staphylococcal infections in intensive care units in the United States, for example, are caused by methicillin-resistant bacterial strains. The incidence of the emerging methicillin-resistant staphylococcus aureus strains in community has raised many concerns. These strains were found to express a wide range of virulence factors ([[https://en.wikipedia.org/wiki/Virulence_factor](https://en.wikipedia.org/wiki/Virulence_factor)]([https://en.wikipedia.org/wiki/Virulence_factor](https://en.wikipedia.org/wiki/Virulence_factor)), accessed on 15 January 2021) and have an enhanced tendency toward progression into invasive ailments. The action takes place over two-step reactions. In the first step, methionine and ATP bind together to the enzyme's active site, resulting in the formation of methionyl adenylate, releasing pyrophosphate (PPi). In the following reaction, the activated methionyl adenylate is moved to tRNAMetat and its 3\({}^{\prime}\) end, releasing an AMP molecule. MetRS has the unique ability to identify and load two tRNA substrates; namely, tRNAMet and tRNAMet [51]. For these reasons, the design of alternative antibacterial agents exhibiting an activity against drug-resistant _staphylococci_ represents an important area for the development of novel drugs. Figure 8: 2D-interactions of compounds **5a**, **5i**, **5i** enantiomer**, Ampicillin and Tetracycline with amino acid residues on glucosamine 6-phosphate synthase (Ijxa). Again, our _in silico_ study results revealed that the screened compounds, except the **5a** enantiomer, exhibited low binding energy when docked into methionyl-trna-synthetase (1 PFV) and shared similar interactions with several amino acids similar to the positive control, Ampicillin and Tetracycline (Table 7) and Figure 9.  
Interestingly, all compounds obeyed to the parameters of the rule of 5 (Lipinski rule) [52]. These include molecular weight, number of hydrogen bonds, accepting (lip_acc) and donating (lip_don) groups, and the drug-likeness potential (Table 8).