Condensation of the corresponding chlorides of some substituted pyrazine-2-carboxylic acids (pyrazine-2-carboxylic acid, 6-chloropyrazine-2-carboxylic acid, 5-tert-butylpyrazine-2-carboxylic acid or 5-tert-butyl-6-chloropyrazine-2-carboxylic acid) with various ring-substituted aminothiazoles or anilines yielded a series of amides. The syntheses, analytical and spectroscopic data of thirty newly prepared compounds are presented. Structure-activity relationships between the chemical structures and the anti-mycobacterial, antifungal and photosynthesis-inhibiting activity of the evaluated compounds are discussed. 3,5-Bromo-4-hydroxyphenyl derivatives of substituted pyrazinecarboxylic acid, 16-18, have shown the highest activity against Mycobacterium tuberculosis H(37)Rv (54-72% inhibition). The highest antifungal effect against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for 5-tert-butyl-6-chloro-N-(4-methyl-1,3-thiazol-2-yl)pyrazine-2-carboxamide (8, MIC =31.25 micromol x mL(-1)). The most active inhibitors of oxygen evolution rate in spinach Molecules 2006, 11,243 chloroplasts were the compounds 5-tert-butyl-6-chloro-N-(5-bromo-2-hydroxyphenyl)- pyrazine-2-carboxamide (27, IC(50) = 41.9 micromol x L(-1)) and 5-tert-butyl-6-chloro-N-(1,3- thiazol-2-yl)-pyrazine-2-carboxamide (4, IC50 = 49.5 micromol x L(-1)).

• MeSH
• amidy chemická syntéza   farmakologie   MeSH
• antibakteriální látky chemická syntéza   farmakologie   MeSH
• antifungální látky chemická syntéza   farmakologie   MeSH
• fotosyntéza účinky léků   MeSH
• kyseliny karboxylové chemie   MeSH
• Mycobacterium tuberculosis účinky léků   MeSH
• pyraziny chemie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• amidy MeSH
• antibakteriální látky MeSH
• antifungální látky MeSH
• kyseliny karboxylové MeSH
• pyraziny MeSH

Unsubstituted, halogenated and/or alkylated pyrazine-2-carboxylic acid amides connected via -CONH- bridge with substituted anilines were synthesized using currently known synthetic pathways. The synthetic approach, analytical, spectroscopic, lipophilicity and biological data of 20 newly synthesized compounds are presented. Structure-activity relationships among the chemical structures, the antimycobacterial, antifungal, photosynthesis inhibiting and antialgal activity of the evaluated substituted N-phenylpyrazine-2-carboxamides are discussed. 5-tert-Butyl-6-chloro-N-(3-trifluoromethylphenyl)pyrazine-2-carboxamide (19) has shown the highest activity against Mycobacterium tuberculosis H(37)Rv (MIC=3.13 microg/mL). The highest antifungal effect against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for N-(3-trifluoromethylphenyl)pyrazine-2-carboxamide (14, MIC=62.5 micromol/mL). The highest reduction of chlorophyll content in Chlorella vulgaris was found for pyrazine-2-carboxylic acid (3-trifluoromethylphenyl)amide (9, IC(50)=12.1 micromol/L).

• MeSH
• amidy chemická syntéza   chemie   farmakologie   MeSH
• antibakteriální látky chemická syntéza   chemie   farmakologie   MeSH
• antifungální látky chemická syntéza   chemie   farmakologie   MeSH
• Cercopithecus aethiops MeSH
• Chlorella vulgaris účinky léků   metabolismus   MeSH
• chlorofyl metabolismus   MeSH
• chloroplasty účinky léků   metabolismus   MeSH
• herbicidy chemická syntéza   chemie   farmakologie   MeSH
• mikrobiální testy citlivosti MeSH
• Mycobacterium tuberculosis účinky léků   MeSH
• pyraziny chemická syntéza   chemie   farmakologie   MeSH
• Spinacia oleracea účinky léků   metabolismus   MeSH
• Vero buňky MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• amidy MeSH
• antibakteriální látky MeSH
• antifungální látky MeSH
• chlorofyl MeSH
• herbicidy MeSH
• pyraziny MeSH

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb), each year causing millions of deaths. In this article, we present the synthesis and biological evaluations of new potential antimycobacterial compounds containing a fragment of the first-line antitubercular drug pyrazinamide (PZA), coupled with methyl or ethyl esters of selected amino acids. The antimicrobial activity was evaluated on a variety of (myco)bacterial strains, including Mtb H37Ra, M. smegmatis, M. aurum, Staphylococcus aureus, Pseudomonas aeruginosa, and fungal strains, including Candida albicans and Aspergillus flavus. Emphasis was placed on the comparison of enantiomer activities. None of the synthesized compounds showed any significant activity against fungal strains, and their antibacterial activities were also low, the best minimum inhibitory concentration (MIC) value was 31.25 µM. However, several compounds presented high activity against Mtb. Overall, higher activity was seen in derivatives containing ʟ-amino acids. Similarly, the activity seems tied to the more lipophilic compounds. The most active derivative contained phenylglycine moiety (PC-ᴅ/ʟ-Pgl-Me, MIC < 1.95 µg/mL). All active compounds possessed low cytotoxicity and good selectivity towards Mtb. To the best of our knowledge, this is the first study comparing the activities of the ᴅ- and ʟ-amino acid derivatives of pyrazinamide as potential antimycobacterial compounds.

• Klíčová slova
• amino acids, antibacterial, antimycobacterial, cytotoxicity, pyrazinamide, tuberculosis,
• MeSH
• aminokyseliny chemie   farmakologie   MeSH
• antibakteriální látky farmakologie   MeSH
• antituberkulotika farmakologie   MeSH
• Aspergillus flavus účinky léků   MeSH
• buňky Hep G2 MeSH
• Candida albicans účinky léků   MeSH
• chromatografie kapalinová MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie MeSH
• mikrobiální testy citlivosti MeSH
• Mycobacterium smegmatis účinky léků   MeSH
• Mycobacterium tuberculosis účinky léků   MeSH
• optická otáčivost MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• Pseudomonas aeruginosa účinky léků   MeSH
• pyrazinamid chemie   farmakologie   MeSH
• Staphylococcus aureus účinky léků   MeSH
• tuberkulóza farmakoterapie   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminokyseliny MeSH
• antibakteriální látky MeSH
• antituberkulotika MeSH
• pyrazinamid MeSH

This paper describes preparation and biological evaluation of pyrazinamide analogues. Pyrazinamide with its simple structure gives a good opportunity for further modification regarding an increase of its antimycobacterial activity. We prepared a series of compounds derived from pyrazine-2,5-dicarbonitrile with arylamino substitution in position 3. All compounds were assayed in vitro against major Mycobacterium and various Fungi species. The best activity was found in 3-{[3-(trifluoromethyl)phenyl]amino}pyrazine-2,5-dicarbonitrile 11 with the value of 6.25 micromol(-1) against M. tuberculosis H(37)Rv and moderate activity against minor Mycobacterium pathogens.

• MeSH
• Absidia účinky léků   MeSH
• antifungální látky chemická syntéza   farmakologie   MeSH
• antituberkulotika chemická syntéza   farmakologie   MeSH
• Aspergillus fumigatus účinky léků   MeSH
• Candida účinky léků   MeSH
• mikrobiální testy citlivosti MeSH
• Mycobacterium účinky léků   MeSH
• nitrily chemická syntéza   farmakologie   MeSH
• pyrazinamid analogy a deriváty   chemická syntéza   farmakologie   MeSH
• pyraziny chemická syntéza   farmakologie   MeSH
• Trichosporon účinky léků   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3-((3-(trifluoromethyl)phenyl)amino)pyrazine-2,5-dicarbonitrile MeSH Prohlížeč
• antifungální látky MeSH
• antituberkulotika MeSH
• nitrily MeSH
• pyrazinamid MeSH
• pyraziny MeSH