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Biomedical subjects

Jirí Kunes

Publications and source records attributed to Jirí Kunes.

11 recordsLinked to original sources
PubMed2006

The oriented development of antituberculotics: salicylanilides.

On the basis of our previous results 22 salicylanilides were synthesized. The compounds were tested for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii, and Mycobacterium avium. The Free-Wilson method was used to evaluate structure-antimycobacterial activity relationships. 4-Chloro-N-(4-propylphenyl)salicylamide and 5-chloro-N-(4-propylphenyl)salicylamide were selected for preclinical studies.

Antitubercular Agents↗
PubMed2005

Heterocyclic isosters of antimycobacterial salicylanilides.

A series of 64 derivatives of substituted heterocyclic analogues of salicylanilides was synthesized. The compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium avium and two strains of Mycobacterium kansasii. For the QSAR study, the combination of Free-Wilson approach with Hansch approach was used. The molecules were separated on the heterocyclic and salicyl moieties and the study of influences of electronic and hydrophobic properties was used as well. The compounds are a new group of potential anti-tuberculotics.

Anti-Bacterial Agents↗
PubMed2005

A note on the antitubercular activities of 1-aryl-5-benzylsulfanyltetrazoles.

A set of 32 1-phenyl-5-benzylsulfanyltetrazoles substituted on the phenyl ring as well as on the benzyl moiety was synthesized. The compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis. The activity against M. tuberculosis becomes higher with increasing electron-accepting properties of the substituents on the phenyl ring. On the other hand, any substitution on the benzylic moiety decreases the activity.

Antitubercular Agents↗
PubMed2004

Neighboring group effect in Pd-catalyzed carbonylation terminated by lactonization: a need for a protective group and/or DMF.

Synthesis of analogues of antifungal podolactones via Pd-catalyzed processes revealed that tandem 6-exo-alkyne carbopalladation/carbonylative lactonization sequence is strongly solvent-dependent. Contrary to earlier reports, premature esterification was the predominant pathway when the starting enynes derived from (Z)-2-iodohex-2-en-1,4-diol were subjected to Pd-catalyzed carbonylation in MeOH. Apparently, irreversible complexation of Pd by the OH group prevented decarbonylation and hence 6-exo-alkyne carbopalladation. Similarly, the influence of the chelation was also evident when the reaction was applied to the analogous preparation of 3-hydroxymethylbutenolides. The neighboring group effect can be efficiently overcome through using DMF as the solvent in combination with protection of the OH function.

Antifungal Agents↗
PubMed2004

Antimycobacterial N-pyridinylsalicylamides, isosters of salicylamides.

The series of derivatives of substituted N-pyridinylsalicylamides were synthesized. The compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium avium and two strains of Mycobacterium kansasii. In the quantitative structure activity relationships analysis (QSAR), the Free-Wilson and Hansch approaches were used but the analysis was not significant. (The standard deviations of regression coefficients were greater than the values of the coefficients). The molecules were separated the heterocyclic and salicyl moiety in the molecules, and the study of influences of substituents on salicyl moiety was used, as well. 5-chloro-pyridin-2-yl, and the substitution of the salicyl moiety by chlorine in position 4 or 5 had the strongest influence on the increase in antimycobacterial activity.

Anti-Bacterial Agents↗
PubMed2003

Synthesis and structure-antifungal activity relationships of 3-aryl-5-alkyl-2,5-dihydrofuran-2-ones and their carbanalogues: further refinement of tentative pharmacophore group.

Two series of 3-(substituted phenyl)-5-alkyl-2,5-dihydrofuran-2-ones related to a natural product, (-)incrustoporine, were synthesized and their in vitro antifungal activity evaluated. The compounds with halogen substituents on the phenyl ring exhibited selective antifungal activity against the filamentous strains of Absidia corymbifera and Aspergillus fumigatus. On the other hand, the influence of the length of the alkyl chain at C(5) was marginal. The antifungal effect of the most active compound against the above strains was higher than that of ketoconazole, and close to that of amphotericin B. In order to verify the hypothesis about a possible relationship between the Michael-accepting ability of the compounds and their antifungal activity, a series of simple carbanalogues, 2-(substituted phenyl)cyclopent-2-enones, was prepared and subjected to antifungal activity assay as well.

4-Butyrolactone↗
PubMed2003

Relationship between the structure and antimycobacterial activity of substituted salicylanilides.

A series of 143 salicylanilides substituted in positions 4 and 5 and in positions 3' and 4' was synthesized. The compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii, and Mycobacterium avium. To describe the structure-antimycobacterial activity relationships (QSARs), an approach based on the combination of the Free-Wilson and Hansch methods was employed (the substituent constants were used in the case of the substituents on the phenyl ring; indicator parameters were used for the substituents on the acyl moiety). The relationships between the antimycobacterial activity and physico-chemical parameters of all substituents were also explored. The quadratic representation of lipophilicity parameters did not lead to significant correlations.

Anti-Bacterial Agents↗
PubMed2003

3-Benzyl-2H-1,3-benzoxazine-2,4(3H)-diones, a new group of antimycobacterial compounds against potentially pathogenic strains.

A series of derivatives of 3-benzyl-2H-benzoxazine-2,4(3H)-dione substituted in positions 6, 7 or 8 on the benzoxazine, and in positions 3 or 4 on the benzyl moiety was synthesized. The compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium avium and two strains of Mycobacterium kansasii. The disadvantage of the compounds is in their low solubility in water. The antimycobacterial activity of N-benzylsalicylamides correlates with that of 3-benzyl-2H-1,3-benzoxazin-2,4(3H)-diones and depends on the partition coefficients and electronic indexes.

Anti-Bacterial Agents↗
PubMed2002

On the relationship between the substitution pattern of thiobenzanilides and their antimycobacterial activity.

The goal of this work was to shed more light on a preliminary finding about the relationship between the substitution in the thioacyl part of thiobenzanilides and their antituberculous effect. Thus, we prepared a set of 14 derivatives, out of which eight had not yet been reported, and the compounds were evaluated for antimycobacterial activity on a panel of four Mycobacteria species, including Mycobacterium tuberculosis CNCTC My 331/88, Mycobacterium kansasii CNCTC My 235/80, Mycobacterium avium CNCTC My 330/88 and M. kansasii 6509/96. While the contribution of the substituents with differing electronic and lipophilicity characteristics in position 3 to the antituberculous activity was negligible, we found that unsubstituted position 4 in the thioacyl part appears to be a prerequisite for a thiobenzanilide derivative to possess appreciable biological activity.

Anilides↗
PubMedDate not supplied

Analytical monitoring of trinitrotoluene metabolites in urine by GC-MS. Part I. Semiquantitative determination of 4-amino-2,6-dinitrotoluene in human urine.

A routine procedure for the monitoring of occupational exposure to 2,4,6-trinitrotoluene (TNT) based on the semiquantitative determination of 4-amino-2,6-dinitrotoluene (4A2,6-DNT) in urine samples by gas chromatography (GC-MS) was developed. For calibration purposes, a standard sample of 4-amino-4,6-dinitrotoluene was prepared. Urine samples were collected from munition workers in a military plant in Hradec Kralove district. The samples were extracted into ethyl acetate, and analyzed by GC-MS without previous derivatization. The GC was equipped with a DB1701 column (30 m, 0.25 mm, 0.25 microm) for optimum separation. 4A2,6-DNT was detected at concentrations above the limit of quantitation (0.2 mg/L). This simple method is sufficient for the screening of high degree of TNT exposure and constitutes the first step of a broad project focused on this occupational medicine problem.

Adult↗