This study evaluates the antimycobacterial potential of novel "mutual" bioactive amides, combining pyridine-4-carbohydrazide (isoniazid, INH) with various antimicrobial agents (sulphonamides, 4-aminosalicylic acid, thiosemicarbazide, diphenyl (thio)ethers) via oxocarboxylic acids. The aim was to enhance activity against both drug-susceptible and multidrug-resistant (MDR) Mycobacterium tuberculosis and non-tuberculous strains, while overcoming drug resistance through dual-action mechanisms. Many derivatives exhibited potent antimycobacterial activity, with minimum inhibitory concentrations (MICs) as low as ≤0.25 μM, outperforming INH, especially diphenyl (thio)ethers and biphenyl analogues. Additionally, the compounds were effective against M. kansasii (MICs ≤1 μM) and inhibited MDR strains at higher concentrations (≥8 μM). The cytotoxicity assay indicated a favourable safety profile, with no significant haemolysis at 125 μM, and some compounds were even protective. Selectivity for mycobacteria was confirmed by low inhibition of Gram-positive bacteria and inactivity against Gram-negative bacteria or fungi, highlighting the potential for further development as antimycobacterial agents.

• Publikační typ
• časopisecké články MeSH

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.

• Klíčová slova
• 4-aminobenzoic acid, Schiff bases, antibacterial activity, antifungal activity, cytotoxicity, synthesis, vitamin,
• MeSH
• antibakteriální látky chemie   farmakologie   MeSH
• buňky Hep G2 MeSH
• cytotoxiny chemie   farmakologie   MeSH
• kyselina 4-aminobenzoová chemie   farmakologie   MeSH
• kyselina listová chemie   farmakologie   MeSH
• lidé MeSH
• methicilin rezistentní Staphylococcus aureus účinky léků   růst a vývoj   MeSH
• mikrobiální testy citlivosti MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• cytotoxiny MeSH
• kyselina 4-aminobenzoová MeSH
• kyselina listová MeSH

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.

• Klíčová slova
• Schiff bases, antibacterial activity, antifungal activity, antimycobacterial activity, cytotoxicity, sulfadiazine, sulfonamides,
• MeSH
• aldehydy chemická syntéza   farmakologie   MeSH
• antibakteriální látky chemická syntéza   chemie   farmakologie   MeSH
• antifungální látky chemická syntéza   chemie   farmakologie   MeSH
• antiinfekční látky chemická syntéza   farmakologie   MeSH
• buňky Hep G2 MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• pyrimidiny chemická syntéza   farmakologie   MeSH
• Schiffovy báze chemická syntéza   farmakologie   MeSH
• sulfadiazin analogy a deriváty   chemická syntéza   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aldehydy MeSH
• antibakteriální látky MeSH
• antifungální látky MeSH
• antiinfekční látky MeSH
• pyrimidiny MeSH
• salicylaldehyde MeSH Prohlížeč
• Schiffovy báze MeSH
• sulfadiazin MeSH

Infections caused by Mycobacterium tuberculosis (Mtb.) and nontuberculous mycobacteria (NTM) are considered to be a global health problem; current therapeutic options are limited. Sulfonamides have exhibited a wide range of biological activities including those against mycobacteria. Based on the activity of 4-(3-heptylureido)-N-(5-methylisoxazol-3-yl)benzenesulfonamide against NTM, we designed a series of homologous sulfamethoxazole-based n-alkyl ureas (C₁-C12), as well as several related ureas and an oxalamide. Fifteen ureas and one oxalamide were synthesized by five synthetic procedures and characterized. They were screened for their activity against Mtb. and three NTM strains (M. avium, M. kansasii). All of them share antimycobacterial properties with minimum inhibitory concentration (MIC) values starting from 2 µM. The highest activity showed 4,4'-[carbonylbis(azanediyl)]bis[N-(5-methylisoxazol-3-yl)benzenesulfonamide] with MIC of 2-62.5 µM (i.e., 1.07-33.28 µg/mL). Among n-alkyl ureas, methyl group is optimal for the inhibition of both Mtb. and NTM. Generally, longer alkyls led to increased MIC values, heptyl being an exception for NTM. Some of the novel derivatives are superior to parent sulfamethoxazole. Several urea and oxalamide derivatives are promising antimycobacterial agents with low micromolar MIC values.

• Klíčová slova
• antimycobacterial activity, in vitro activity, oxalamide, sulfamethoxazole, sulfonamides, tuberculosis, ureas,
• MeSH
• antibakteriální látky chemická syntéza   chemie   farmakologie   MeSH
• mikrobiální testy citlivosti MeSH
• močovina chemická syntéza   chemie   farmakologie   MeSH
• molekulární struktura MeSH
• Mycobacterium účinky léků   MeSH
• sulfamethoxazol chemická syntéza   chemie   farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• močovina MeSH
• sulfamethoxazol MeSH