Current Perspectives on Biological Screening of Newly Synthetised Sulfanilamide Schiff Bases as Promising Antibacterial and Antibiofilm Agents

Abstract

Growing resistance to antimicrobials, combined with pathogens that form biofilms, presents significant challenges in healthcare. Modifying current antimicrobial agents is an economical approach to developing novel molecules that could exhibit biological activity. Thus, five sulfanilamide Schiff bases were synthesized under microwave irradiation and characterized spectroscopically and in silico. They were evaluated for their antimicrobial and antibiofilm activities against both Gram-positive and Gram-negative bacterial strains. Their cytotoxic potential against two cancer cell lines was also determined. Gram-positive bacteria were susceptible to the action of these compounds. Derivatives 1b and 1d inhibited S. aureus's growth (MIC from 0.014 mg/mL) and biofilm (IC from 0.029 mg/mL), while compound 1e was active against E. faecalis's planktonic and sessile forms. Two compounds significantly reduced cell viability at 5 μg/mL after 24 h of exposure (1d-HT-29 colorectal adenocarcinoma cells, 1c-LN229 glioblastoma cells). A docking study revealed the increased binding affinities of these derivatives compared to sulfanilamide. Hence, these Schiff bases exhibited higher activity compared to their parent drug, with halogen groups playing a crucial role in both their antimicrobial and cytotoxic effects.

Keywords: Schiff base; antibiofilm; antimicrobial; cytotoxicity; sulfanilamide.

Figure 2

Structure–activity relationship of selected sulfonamide-derived Schiff bases’ anticancer (CA inhibition) effect [20,21,22,29,30].

Figure 1

Structure–activity relationship of selected sulfonamide-derived Schiff bases’ antimicrobial effect [15,16,17,18,19].

Scheme 1

Preparation of sulfanilamide Schiff base derivatives 1a–e. Radical R is: 4-PhO (a); 2-Br (b); 2,6-diCl (c); 3,5-diCl (d); 2,3,5-triCl (e).

Figure 3

Comparative docking scores of Schiff bases 1a–e for 1AJ0 and 1AD4. * Calculated using the CLC Drug Discovery Workbench, ** Calculated using the Molegro Virtual Docker.

Figure 4

Interactions between compounds 1b, 1d, 1e and the amino acids of the active site of E. coli DHPTS (1AJ0). (a) Hydrogen bonds of 1b (CLC Drug Discovery Workbench); (b) hydrogen bonds (blue) and steric interactions (red) of 1b (Molegro Virtual Docker); (c) hydrogen bonds of 1d (CLC Drug Discovery Workbench); (d) hydrogen bonds (blue) and steric interactions (red) of 1d (Molegro Virtual Docker); (e) hydrogen bonds of 1e (CLC Drug Discovery Workbench); (f) hydrogen bonds (blue) and steric interactions (red) of 1e (Molegro Virtual Docker).

Figure 4

Interactions between compounds 1b, 1d, 1e and the amino acids of the active site of E. coli DHPTS (1AJ0). (a) Hydrogen bonds of 1b (CLC Drug Discovery Workbench); (b) hydrogen bonds (blue) and steric interactions (red) of 1b (Molegro Virtual Docker); (c) hydrogen bonds of 1d (CLC Drug Discovery Workbench); (d) hydrogen bonds (blue) and steric interactions (red) of 1d (Molegro Virtual Docker); (e) hydrogen bonds of 1e (CLC Drug Discovery Workbench); (f) hydrogen bonds (blue) and steric interactions (red) of 1e (Molegro Virtual Docker).

Figure 5

Interactions between compounds 1b, 1d, 1e and the amino acids of the active site of S. aureus DHPTS (1AD4). (a) Hydrogen bonds of 1b (CLC Drug Discovery Workbench); (b) hydrogen bonds (blue) and steric interactions (red) of 1b (Molegro Virtual Docker); (c) hydrogen bonds of 1d (CLC Drug Discovery Workbench); (d) hydrogen bonds (blue) and steric interactions (red) of 1d (Molegro Virtual Docker); (e) hydrogen bonds of 1e (CLC Drug Discovery Workbench); (f) hydrogen bonds (blue) and steric interactions (red) of 1e (Molegro Virtual Docker).

Figure 5

Interactions between compounds 1b, 1d, 1e and the amino acids of the active site of S. aureus DHPTS (1AD4). (a) Hydrogen bonds of 1b (CLC Drug Discovery Workbench); (b) hydrogen bonds (blue) and steric interactions (red) of 1b (Molegro Virtual Docker); (c) hydrogen bonds of 1d (CLC Drug Discovery Workbench); (d) hydrogen bonds (blue) and steric interactions (red) of 1d (Molegro Virtual Docker); (e) hydrogen bonds of 1e (CLC Drug Discovery Workbench); (f) hydrogen bonds (blue) and steric interactions (red) of 1e (Molegro Virtual Docker).

Figure 6

Minimum inhibitory concentration (MIC) values of the compounds (mean ± SD) against (a) Staphylococcus aureus ATCC 25923; (b) Enterococcus faecalis ATCC 29212; (c) Escherichia coli ATCC 25922; and (d) Pseudomonas aeruginosa ATCC 27853. Corresponding notations: S (sulfanilamide).

Figure 7

Minimum inhibitory concentrations against bacterial adherence to the inert substrata of the tested compounds (mean ± SD): (a) Staphylococcus aureus ATCC 25923; (b) Enterococcus faecalis ATCC 29212; (c) Escherichia coli ATCC 25922; (d) Pseudomonas aeruginosa ATCC 27853. Corresponding notations: S (Sulfanilamide).

Figure 8

Graphical representation of the HT-29 adenocarcinoma cells’ viability after 24 h and 48 h exposure to sulfanilamide, 1a, 1b, 1c, 1d and 1e treatments at 1 mg/mL, 500 μg/mL, 200 μg/mL, 50 μg/mL, 40 μg/mL, 8 μg/mL, 5 μg/mL and 1.6 μg/mL, as compared to untreated cells (**** = p < 0.0001 sample versus untreated cells; *** = p < 0.001 sample versus untreated cells and ** = p < 0.01 sample versus untreated cells).

Figure 9

Graphical representation of the LN229 glioblastoma cells’ viability after 24 h and 48 h exposure to sulfanilamide, 1a, 1b, 1c, 1d and 1e treatments at 1mg/mL, 500 μg/mL, 200 μg/mL, 50 μg/mL, 40 μg/mL, 8 μg/mL, 5 μg/mL and 1.6 μg/mL, as compared to untreated cells (**** = p < 0.0001 sample versus untreated cells; *** = p < 0.001 sample versus untreated cells, ** = p < 0.01 sample versus untreated cells and * = p < 0.05 sample versus untreated cells).