A series of twelve amides was synthesized via aminolysis of substituted pyrazinecarboxylic acid chlorides with substituted benzylamines. Compounds were characterized with analytical data and assayed in vitro for their antimycobacterial, antifungal, antibacterial and photosynthesis-inhibiting activity. 5-tert-Butyl-6-chloro-N-(4-methoxybenzyl)pyrazine-2-carboxamide (12) has shown the highest antimycobacterial activity against Mycobacterium tuberculosis (MIC = 6.25 µg/mL), as well as against other mycobacterial strains. The highest antifungal activity against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for 5-chloro-N-(3-trifluoromethylbenzyl)-pyrazine-2-carboxamide (2, MIC = 15.62 µmol/L). None of the studied compounds exhibited any activity against the tested bacterial strains. Except for 5-tert-butyl-6-chloro-N-benzylpyrazine-2-carboxamide (9, IC(50) = 7.4 µmol/L) and 5-tert-butyl-6-chloro-N-(4-chlorobenzyl)pyrazine-2-carboxamide (11, IC(50) = 13.4 µmol/L), only moderate or weak photosynthesis-inhibiting activity in spinach chloroplasts (Spinacia oleracea L.) was detected.

• MeSH
• Amides chemical synthesis   pharmacology   MeSH
• Antifungal Agents chemical synthesis   pharmacology   MeSH
• Antibiotics, Antitubercular chemical synthesis   pharmacology   MeSH
• Chloroplasts drug effects   metabolism   MeSH
• Photosynthesis drug effects   MeSH
• Herbicides chemical synthesis   pharmacology   MeSH
• Hydrophobic and Hydrophilic Interactions MeSH
• Microbial Sensitivity Tests MeSH
• Mycobacterium tuberculosis drug effects   MeSH
• Pyrazines chemical synthesis   pharmacology   MeSH
• Spinacia oleracea drug effects   metabolism   MeSH
• Trichophyton drug effects   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Amides MeSH
• Antifungal Agents MeSH
• Antibiotics, Antitubercular MeSH
• Herbicides MeSH
• Pyrazines MeSH

The effect of new synthetic pyrazinecarboxamide derivatives as potential elicitors of flavonolignan and flavonoid production in Silybum marianum and Ononis arvensis cultures in vitro was investigated. Both tested elicitors increased the production of flavonolignans in S. marianum callus and suspension cultures and flavonoids in O. arvensis callus and suspension cultures. Compound I, 5-(2-hydroxybenzoyl)-pyrazine-2-carboxamide, has shown to be an effective elicitor of flavonolignans and taxifoline production in Silybum marianum culture in vitro. The maximum content of silydianin (0.11%) in S. marianum suspension culture was induced by 24 h elicitor application in concentration of 1.159 × 10⁻³ mol/L. The maximum content of silymarin complex (0.08%) in callus culture of S. marianum was induced by 168 h elicitor application of a concentration 1.159 × 10⁻⁴ mol/L, which represents contents of silydianin (0.03%), silychristin (0.01%) and isosilybin A (0.04%) compared with control. All three tested concentrations of compound II, N-(2-bromo-3-methylphenyl)-5-tert-butylpyrazin-2-carboxamide increased the flavonoid production in callus culture of O. arvensis in a statistically significant way. The best elicitation effect of all elicitor concentrations had the weakest c₃ concentration (8.36 × 10⁻⁶ mol/L) after 168 h time of duration. The maximum content of flavonoids (about 5,900%) in suspension culture of O. arvensis was induced by 48 h application of c₃ concentration (8.36 × 10⁻⁶ mol/L).

• MeSH
• Amides * chemistry   pharmacology   MeSH
• Fabaceae chemistry   cytology   metabolism   MeSH
• Flavonoids biosynthesis   chemistry   MeSH
• Flavonolignans biosynthesis   chemistry   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Molecular Structure MeSH
• Silybum marianum chemistry   cytology   metabolism   MeSH
• Pyrazines * chemistry   pharmacology   MeSH
• Plant Extracts chemistry   pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Amides * MeSH
• Flavonoids MeSH
• Flavonolignans MeSH
• Pyrazines * MeSH
• Plant Extracts MeSH

A series of sixteen pyrazinamide analogues with the -CONH- linker connecting the pyrazine and benzene rings was synthesized by the condensation of chlorides of substituted pyrazinecarboxylic acids with ring-substituted (chlorine) anilines. The prepared compounds were characterized and evaluated for their antimycobacterial and antifungal activity, and for their ability to inhibit photosynthetic electron transport (PET). 6-Chloro-N-(4-chlorophenyl)pyrazine-2-carboxamide manifested the highest activity against Mycobacterium tuberculosis strain H37Rv (65% inhibition at 6.25 μg/mL). The highest antifungal effect against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for 6-chloro-5-tert-butyl-N-(3,4-dichlorophenyl)pyrazine-2-carboxamide (MIC=62.5 μmol/L). 6-chloro-5-tert-butyl-N-(4-chlorophenyl)pyrazine-2-carboxamide showed the highest PET inhibition in spinach chloroplasts (Spinacia oleracea L.) chloroplasts (IC50=43.0 μmol/L). For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds as well as their structure-activity relationships are discussed.

• MeSH
• Anti-Bacterial Agents * chemical synthesis   chemistry   pharmacology   MeSH
• Antifungal Agents * chemical synthesis   chemistry   pharmacology   MeSH
• Chloroplasts metabolism   MeSH
• Hydrocarbons, Chlorinated chemical synthesis   chemistry   pharmacology   MeSH
• Photosynthesis drug effects   MeSH
• Molecular Structure MeSH
• Mycobacterium tuberculosis growth & development   MeSH
• Pyrazinamide * analogs & derivatives   chemical synthesis   chemistry   pharmacology   MeSH
• Spinacia oleracea metabolism   MeSH
• Trichophyton growth & development   MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Bacterial Agents * MeSH
• Antifungal Agents * MeSH
• Hydrocarbons, Chlorinated MeSH
• Pyrazinamide * MeSH

In this study, series of ring-substituted 2-styrylquinazolin-4(3H)-one and 4-chloro-2-styrylquinazoline derivatives were prepared. The syntheses of the discussed compounds are presented. The compounds were analyzed by RP-HPLC to determine lipophilicity. They were tested for their inhibitory activity on photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Primary in vitro screening of the synthesized compounds was also performed against four mycobacterial strains and against eight fungal strains. Several compounds showed biological activity comparable with or higher than that of the standard isoniazid. It was found that the electronic properties of the R substituent, and not the total lipophilicity of the compound, were decisive for the photosynthesis-inhibiting activity of tested compounds.

• MeSH
• Antitubercular Agents chemical synthesis   chemistry   pharmacology   MeSH
• Mycobacterium Infections, Nontuberculous drug therapy   MeSH
• Pneumonia, Bacterial drug therapy   microbiology   MeSH
• Quinazolines chemical synthesis   chemistry   pharmacology   MeSH
• Chloroplasts drug effects   MeSH
• Photosynthesis drug effects   MeSH
• Humans MeSH
• Nontuberculous Mycobacteria drug effects   MeSH
• Spinacia oleracea drug effects   MeSH
• Styrenes chemical synthesis   pharmacology   MeSH
• Electron Transport drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 2-styrylquinazolin-4(3H)-one MeSH Browser
• 4-chloro-2-styrylquinazoline MeSH Browser
• Antitubercular Agents MeSH
• Quinazolines MeSH
• Styrenes MeSH
• styrylquinazoline MeSH Browser

In the study, a series of twelve ring-substituted 4-hydroxy-1H-quinolin-2-one derivatives were prepared. The procedures for synthesis of the compounds are presented. The compounds were analyzed using RP-HPLC to determine lipophilicity and tested for their photosynthesis-inhibiting activity using spinach (Spinacia oleracea L.) chloroplasts. All the synthesized compounds were also evaluated for antifungal activity using in vitro screening with eight fungal strains. For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed, as well as their structure-activity relationships (SAR).

• MeSH
• Antifungal Agents chemistry   MeSH
• Quinolones chemical synthesis   pharmacology   MeSH
• Chloroplasts drug effects   MeSH
• Photosynthesis drug effects   MeSH
• Fungi drug effects   MeSH
• Hydrophobic and Hydrophilic Interactions MeSH
• Hydroxyquinolines chemical synthesis   pharmacology   MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antifungal Agents MeSH
• Quinolones MeSH
• Hydroxyquinolines MeSH

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
• Amides chemical synthesis   pharmacology   MeSH
• Anti-Bacterial Agents chemical synthesis   pharmacology   MeSH
• Antifungal Agents chemical synthesis   pharmacology   MeSH
• Photosynthesis drug effects   MeSH
• Carboxylic Acids chemistry   MeSH
• Mycobacterium tuberculosis drug effects   MeSH
• Pyrazines chemistry   MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Amides MeSH
• Anti-Bacterial Agents MeSH
• Antifungal Agents MeSH
• Carboxylic Acids MeSH
• Pyrazines MeSH