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.

4-aminobenzoic acid (PABA), an essential nutrient for many human pathogens, but dispensable for humans, and its derivatives have exhibited various biological activities. In this study, we combined two pharmacophores using a molecular hybridization approach: this vitamin-like molecule and various aromatic aldehydes, including salicylaldehydes and 5-nitrofurfural, via imine bond in one-step reaction. Resulting Schiff bases were screened as potential antimicrobial and cytotoxic agents. The simple chemical modification of non-toxic PABA resulted in constitution of antibacterial activity including inhibition of methicillin-resistant Staphylococcus aureus (minimum inhibitory concentrations, MIC, from 15.62 µM), moderate antimycobacterial activity (MIC ≥ 62.5 µM) and potent broad-spectrum antifungal properties (MIC of ≥ 7.81 µM). Some of the Schiff bases also exhibited notable cytotoxicity for cancer HepG2 cell line (IC₅₀ ≥ 15.0 µM). Regarding aldehyde used for the derivatization of PABA, it is possible to tune up the particular activities and obtain derivatives with promising bioactivities.

Salicylanilides have been a subject of interest in medicinal chemistry as a group with a wide range of biological activities. The antibacterial (including antimycobacterial) and antifungal activities have come to be viewed as very significant. The synthesis of new prodrugs to counter a number of problematic properties of salicylanilides is a current trend. This article brings together the known basic facts about these prodrugs, particularly about the different mechanisms of the antimicrobial action of salicylanilides, including salicylanilide toxicity and undesired effects. The largest part of this group consists of antimicrobial salicylanilide esters with different organic acids, e.g. acetates, carbamates, esters with N-protected amino acids, and mutual antibacterial compounds with known antibacterial agents (β-lactames and linezolid), with the activity and structure-activity relationships of these compounds being of particular interest. This review summarizes the activity of salicylanilides as potential virulence inhibitors attributable to a blockade of the type III secretion pathway. Many salicylanilide ester derivatives have been demonstrated an effective and promising treatment against pathogenic fungi and bacteria (especially against Gram-positive, tuberculous and atypical mycobacterial strains), including strains such as methicillinresistant Staphylococcus aureus and isoniazid-resistant mycobacteria which are resistant to one or more clinically used drugs.