Sulfadiazine Salicylaldehyde-Based Schiff Bases: Synthesis, Antimicrobial Activity and Cytotoxicity

Abstract

The resistance among microbes has brought an urgent need for new drugs. Thus, we synthesized a series of Schiff bases derived from the sulfa drug sulfadiazine and various salicylaldehydes. The resulting 4-[(2-hydroxybenzylidene)amino]-N-(pyrimidin-2-yl)benzene-sulfonamides were characterized and evaluated against Gram-positive and Gram-negative bacteria, yeasts, moulds, Mycobacterium tuberculosis, nontuberculous mycobacteria (M. kansasii, M. avium) and their cytotoxicity was determined. Among bacteria, the genus Staphylococcus, including methicillin-resistant S. aureus, showed the highest susceptibility, with minimum inhibitory concentration values from 7.81 µM. The growth of Candida sp. and Trichophyton interdigitale was inhibited at concentrations starting from 1.95 µM. 4-[(2,5-Dihydroxybenzylidene)amino]-N-(pyrimidin-2-yl)-benzenesulfonamide was identified as the most selective Schiff base for these strains with no apparent cytotoxicity and a selectivity index higher than 16. With respect to M. tuberculosis and M. kansasii that were inhibited within the range of 8 to 250 µM, unsubstituted 4-[(2-hydroxy-benzylidene)amino]-N-(pyrimidin-2-yl)benzenesulfonamide meets the selectivity requirement. In general, dihalogenation of the salicylic moiety improved the antibacterial and antifungal activity but also increased the cytotoxicity, especially with an increasing atomic mass. Some derivatives offer more advantageous properties than the parent sulfadiazine, thus constituting promising hits for further antimicrobial drug development.

Assessment of biological activities of chitosan Schiff base tagged with medicinal plants

“…Furthermore, a prominent peak appears in the spectra of Schiff base at 1654 cm −1 confirmed the formation of an imine (CN) linkage. Similar peaks were found in the literature of the Schiff base compounds …”

4-Aminobenzoic Acid Derivatives: Converting Folate Precursor to Antimicrobial and Cytotoxic Agents

“…These substituents provide both wide-spectrum antibacterial activity and comparatively low MIC values. Interestingly, similar results were obtained for sulfadiazine Schiff bases previously [20]. MIC of 5-nitrofurfural-derived Schiff base 1r (62.5-125 µM, i.e., 16.25-32.51 µg/mL) is fully comparable to breakpoint of its clinically used analogue nitrofurantoin for staphylococci (32-64 µg/mL) according to EUCAST [33].…”

“…Previously, we have applied molecular hybridization approach successfully. Illustratively, salicylaldehyde-based imines and hydrazones derived from known bioactive scaffolds (Figure 2, XIII-XIV) have exhibited a significant antimicrobial activity [19][20][21]. We have described that a potent antimicrobial activity is associated only with the salicylidene moiety and its isomers are substantially less active [21,22].…”

Evaluation of anti-tuberculosis activity of some oxotitanium(IV) Schiff base complexes; molecular docking, dynamics simulation and ADMET studies

“…Many of the Schiff base metal complexes act as antifungal, antibacterial [7], antiviral [8], herbicidal [9], analgesic [10], anti-inflammation [11,12], antioxidant [6,13], antitumor [14,15], anticancer [16,17], antitubercular [18][19][20] agent. Previously, many investigations have been demonstrated that, Schiff base with aromatic and hetarocyclic ring coordinated with transitional metals show potential activity against MTB and different microorganisms [18,[20][21][22][23][24], suggesting new possible candidate to break the resistant of MTB. Synthesis, characterization and biomedical application of our investigated ligands and complexes were reported in our previous work [25].…”