## 3 Discussion  
Over time, resistance of human pathogens to major antibiotics increases, and infectious agents that are resistant to most available antibiotics are rising globally [72]. An important strategy to help prevent and confront the resistance problem requires the discovery and development of new bioactive agents against both planktonic and adherent microorganisms. Medical devices and instruments are prone to microbial colonization and biofilm formation. Therefore, the discovery of agents that could prevent biofilm formation or adherence would be of great use. Very recently, we reported on the synthesis and antimicrobial and antibofilm evaluation results of a series of compounds derived from valine [73; 74]. In the present research, we examined the potential antimicrobial activity of some 1,3-oxazole derivatives and their isostees sharing a 4-(4-X-phenylsulfonyl)phenyl moiety, which were synthesized using two other natural \(\alpha\)-amino acids as raw materials, namely alanine and phenylalanine. Preliminary qualitative antimicrobial screening revealed that compounds **1a-f**; **2a-f**; **3a**; **4a-f**; **5a,b**; **5d,e**; **5g,h**; **5j,k**; **5m,n**; **6g-k**; **6m**; and **6o,p** exhibited inhibitory growth effects, although the growth inhibition zones were detected only in contact with the agar layer. These compounds were further evaluated in vitro to determine their effects on planktonic and adherent microbial growth. Compounds **1a-c**; **4b-f**; **5a,b**; **5d,e**; **5g,h**; **5j,k**; **5m,n**; **6g,h**; **6k**; **6m**; and 6o,p** did not exhibit growth inhibitory effects on any of the tested microbial strains up to a concentration of 225 \(\mu\)g/mL. Regarding the _S. epidermidis_ 756 strain, among the different compounds, **1e,f**; **2d**; and **4a** were the most effective with an MIC of 56.2 \(\mu\)g/mL. The most active compound against _P. aeruginosa_ ATCC 27853 was **3a**, the compounds **1d,e**; **3a**; and **6i,j** were active against C. _albicans_ 128 with a low MIC value of 14 \(\mu\)g/mL, and the compounds **1d,e**; **2a-c**; and **2e,f** proved to be active against _E. coli_ ATCC 25922 with an MIC of 28.1 \(\mu\)g/mL. Regarding _B. subtilis_ ATCC 6683, compound **4a** was found to be the best with an MIC of 56.2 \(\mu\)g/mL, while **3a** had an MIC of 14 \(\mu\)g/mL against _P. aeruginosa_ ATCC 27853. The analyzed compounds affected the adherence and biofilm formation on inert surfaces at MBIC values in the range of 14-225 \(\mu\)g/mL. Our data demonstrated that compounds **1e**, **2d-f**, **4a**, and **6i** had a distinctly stronger effect on _P. aeruginosa_ ATCC 27853 cells embedded in the biofilm (MBIC of 14 \(\mu\)g/mL) than on planktonic cells. We hypothesized that the tested compounds have a specific nonbactericidal mechanism that changes the bacterial cell surface rather than destroying the bacterial cell. From the results obtained in the quantitative screening, it was observed that 2-[4-(4-X-phenylsulfonyl)benzamido]propanoic acids **1a-c** were inactive at the concentrations used in the assay. However, by intramolecular cyclodehydration, biologically active 4_H_-1,3-oxazol-5-ones **2a-c** were obtained, which displayed growth-inhibitory action with an MIC of 28.1 \(\mu\)g/mL and had an antibiofilm effect on _E. coli_ ATCC 25922 with MBIC values of 56.2 (**2b** and **2c**) and 225 (**2a**) \(\mu\)g/mL. The in silico prediction of the pharmacokinetic profile (ADME properties) indicated that compounds **2a-c** had good pharmacokinetic profiles. Compounds **1a-d**, **2a**, and **2d** were predicted to inhibit peptidoglycan glycosyltransferase. By opening the 4_H_-1,3-oxazol-5-ones ring, the resulting \(N\)-acyl-\(\alpha\)-amino ketones (**5a-i**) did not show antimicrobial properties up to a concentration of 225 \(\mu\)g/mL.