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.
- 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
x
- MeSH
- Escherichia coli účinky léků MeSH
- europium MeSH
- penetrační peptidy * MeSH
- Schiffovy báze * chemická syntéza MeSH
- spektrofotometrie statistika a číselné údaje MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice statistika a číselné údaje MeSH
- terbium MeSH
- Publikační typ
- práce podpořená grantem MeSH
N-Unsubstituted indazoles 3 and 1-arylindazoles 4 are readily available in good to high yields through [3+2] cycloaddition of 2-(trimethylsilyl)aryl triflates 1 and diazo compounds in the presence of KF or CsF under mild reaction conditions. Furthermore, we found that azomethine imides also underwent cycloaddition reaction with 2-(trimethylsilyl)phenyl triflates (1a) in the presence of KF to afford indazolone derivatives 6 in moderate yields.
