The condensation of substituted pyrazine-2-carboxylic acid chlorides with ring-substituted anilines yielded five substituted pyrazine-2-carboxylic acid amides. Thesynthesis, and analytical, lipophilicity and biological data of the newly synthesizedcompounds are presented in this paper. The photosynthesis inhibition, antialgal activityand the effect of a series of pyrazine derivatives as abiotic elicitors on the accumulation offlavonoids in a callus culture of Ononis arvensis (L.) were investigated. The most activeinhibitor of the oxygen evolution rate in spinach chloroplasts was 6-chloro-pyrazine-2-carboxylic acid (3-iodo-4-methylphenyl)-amide (2, IC(50) = 51.0 micromol.L(-1)). The highestreduction of chlorophyll content in Chlorella vulgaris was found for 5-tert-butyl-N-(4-chloro-3-methylphenyl)-pyrazine-2-carboxamide (3, IC(50) = 44.0 micromol.L(-1)). The maximalflavonoid production (about 900%) was reached after a twelve-hour elicitation processwith 6-chloropyrazine-2-carboxylic acid (3-iodo-4-methylphenyl)-amide (2).

Department of Pharmaceutical Chemistry and Drug Control Faculty of Pharmacy in Hradec Králové Charles University Prague Heyrovského 1203 Hradec Králové 500 05 Czech Republic

See more in PubMed

Angelova Z., Georgiev S., Roos W. Elicitation of plants. Biotechnol. Biotechnol. Eq. 2006;20:72–83. doi: 10.1080/13102818.2006.10817345. DOI

Dolezal M. Biological active pyrazines of natural and synthetic origin. Chem. Listy. 2006;100:959–966.

Dolezal M., Palek L., Vinsova J., Buchta V., Jampilek J., Kralova K. Substituted Pyrazinecarboxamides; Synthesis and Their Biological Evaluation. Molecules. 2006;11:242–256. doi: 10.3390/11040242. PubMed DOI PMC

Dolezal M., Cmedlova P., Palek L., Vinsova J., Kunes J., Buchta V., Jampilek J., Kralova K. Synthesis and antimycobacterial evaluation of substituted pyrazinecarboxamides. Eur. J. Med. Chem. 2008;43 in press. PubMed

Janin Y. L. Antituberculosis drugs: Ten years of research. Bioorg. Med. Chem. 2007;15:2479–2513. doi: 10.1016/j.bmc.2007.01.030. PubMed DOI

Tripathi R. P., Tewari N., Dwivedi N., Tiwari V. K. Fighting tuberculosis: An old disease with new challenges. Med. Res. Rev. 2005;25:93–131. doi: 10.1002/med.20017. PubMed DOI

Ricci D., Maggiali C.A., Ronchini F., Tirillini B., Fraternale D. Phytochemistry. 1991;30:2821–2824. doi: 10.1016/S0031-9422(00)98205-0. DOI

Camper N. D., McDonald S. K. Tissue and cell cultures as model system in herbicide research. Rev. Weed Sci. 1989;4:169–190.

Linsmaier E., Skoog F. Organic growth factor requirements of tobacco tissue cultures. Physiol. Plant. 1965;18:100–127. doi: 10.1111/j.1399-3054.1965.tb06874.x. DOI

Schmitz R. V., Skoog F., Hecht S. M., Leonard N. J. Comparison of zeatin indoleacetate with zeatin and indoleacetic acid in tobacco bioassay. Plant. Physiol. 1972;50:114–116. doi: 10.1104/pp.50.1.114. PubMed DOI PMC

Huffman J. B., Camper N. D. Growth inhibition in tobacco (Nicotiana tabacum) callus by 2,6-dinitroaniline herbicides and protection by D-α-tocopherol acetate. Weed Sci. 1978;26:527–530.

Tumova L., Ostrozlik P. Ononis arvensis in vitro - Abiotic elicitation. Cesk. Slov. Farm. 2002;51:173–176. PubMed

Tumova L., Gallova K., Rimakova J., Dolezal M., Tuma J. The effect of substituted amides of pyrazine-2-carboxylic acids on flavolignan production in Silybum marianum culture in vitro. Acta Physiol. Plant. 2005;27:357–362.

Dolezal M., Kralova K., Sersen F., Miletin M. The site of action of some anilides of pyrazine-2-carboxylic acids in the photosynthetic apparatus. Folia Pharm. Univ. Carol. 2001;26:13–20.

Abe Y., Shigeta Y., Uchimaru F., Okada S., Ozasayama E. 69 12,898. Japanese Patent. 1969 [Chem. Abstr. 1969, 71, 112979y]

Dolezal M., Hartl J., Miletin M., Machacek M., Kralova K. Chem. Pap. 1999;53:126–128.

Walker D. A. In: Methods in Enzymology Part C. Colowick S.P., Kaplan N.O., editors. Vol. 69. Academic Press; New York: 1980. pp. 94–104.

Kralova K., Sersen F., Sidoova E. Photosynthesis inhibition produced by 2-alkylthio-6-R-benzothiazoles. Chem. Pap. 1992;46:348–350.

Fedke C. Biochemistry and Physiology of Herbicide Action. Springer Verlag; Berlin-Heidelberg-New York: 1982.

Kralova K., Sersen F., Melnik M. Inhibition of photosynthesis in Chlorella vulgaris by Cu(II) complexes with biologically active ligands. J. Trace Microprobe Techn. 1998;16:491–500.

Wellburn A. R. The spectral determination of chlorophyll-A and chlorophyll-B, as well as total carotenoids, using various solvents with spectrophotometers of different resolution. J. Plant. Physiol. 1994;144:307–313. doi: 10.1016/S0176-1617(11)81192-2. DOI

Murashige T., Skoog F. A revised medium for rapid growth and bioassays with tobacco tissue cultures. Physiol. Plant. 1962;15:473–479. doi: 10.1111/j.1399-3054.1962.tb08052.x. DOI

Czech Pharmacopea 1997. Grada; Prague: 1997. p. 1491.

Ureidopyrazine Derivatives: Synthesis and Biological Evaluation as Anti-Infectives and Abiotic Elicitors

New Synthetic Pyrazine Carboxamide Derivatives as Potential Elicitors in Production of Secondary Metabolite in In vitro Cultures

N-substituted 5-amino-6-methylpyrazine-2,3-dicarbonitriles: microwave-assisted synthesis and biological properties

Substituted N-benzylpyrazine-2-carboxamides: synthesis and biological evaluation

Pyrazinecarboxamides as potential elicitors of flavonolignan and flavonoid production in Silybum marianum and Ononis arvensis cultures in vitro

Investigating spectrum of biological activity of 4- and 5-chloro-2-hydroxy-N-[2-(arylamino)-1-alkyl-2-oxoethyl]benzamides

Synthesis, antimycobacterial, antifungal and photosynthesis-inhibiting activity of chlorinated N-phenylpyrazine-2-carboxamides

Substituted pyrazinecarboxamides as abiotic elicitors of flavolignan production in Silybum marianum (L.) gaertn cultures in vitro

Substituted N-Phenylpyrazine-2-carboxamides: synthesis and antimycobacterial evaluation