Biomedical subjects

Jarmila Kaustová

Publications and source records attributed to Jarmila Kaustová.

14 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↗

PubMed2005

[Microbiological diagnosis of mycobacterioses caused by Mycobacterium haemophilum].

INTRODUCTION: According to foreign literature Mycobacterium haemophilum causes diseases of the skin, subcutis and lymph nodes in immunocompetent individuals, while in AIDS patients and in subjects after kidney transplantations it is responsible for osteomyelitis and disseminated infections. MATERIAL AND METHODS: The authors tested the possibility of using a BioFM medium with the X-factor for the detection of Mycobacterium haemophilum in clinical samples and Middlebrook's 7H9 medium with ADC and the X-factor to establish the sensitivity of strains to antimicrobials using the MIC method. CONCLUSIONS: Given the favourable results of preliminary tests the use of the BioFM medium was included among the routine methods applied at the department. In one year Mycobacterium haemophilum was detected with this method in 3 patients presenting extrapulmonary mycobacteriosis.

Adult↗

PubMed2004

Synthesis and antimycobacterial activity of pyridylmethylsulfanyl and naphthylmethylsulfanyl derivatives of benzazoles, 1, 2, 4-triazole, and pyridine-2-carbothioamide/-2-carbonitrile.

A set of four types of benzazoles, 1, 2, 4-triazole, and pyridine-2-carbonitrile/-2-carbothioamide substituted with 1-naphthylmethylsulfanyl or pyridylmethylsulfanyl was prepared to modify the structure of benzylsulfanyl derivatives of the above-mentioned heterocycles. The compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, M. avium, and two strains of M. kansasii. The activities were expressed as the minimum inhibitory concentration (MIC). The MIC values fall into a range of 2 to >1000 micromol/L. Introduction of a pyridyl moiety into the molecule mostly decreased the activity. A naphthyl moiety did not influence the activity in comparison with a phenyl. The most active substances were 4-(3-pyridylmethylsulfanyl)pyridine-2-carbothioamide (7b) (MIC = 2 - >62.5 micromol/L) and 4-(1-naphthylmethylsulfanyl)pyridine-2-carbothioamide (7d) (MIC = 2 - >32 micromol/L).

Anti-Bacterial Agents↗

PubMed2004

Synthesis and antimycobacterial activity of 1,2,4-triazole 3-benzylsulfanyl derivatives.

Series of 3-benzylsulfanyl derivatives of 1,2,4-triazole and 4-methyl-1,2,4-triazole were synthesized by alkylation of starting triazole-3-thiol with appropriately substituted benzyl halide. All members of the set were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, M. avium, and two strains of M. kansasii. The activities were expressed as the minimum inhibitory concentration. The compounds exhibited only a moderate or slight antimycobacterial activity. Minimum inhibitory concentrations fall into a range of 32->1000 micromol/l. The most active substances bear two nitro groups or a thioamide group on the benzyl moiety. As regards the cytotoxicity effect, the evaluated compounds can be considered as moderately toxic.

Anti-Bacterial 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

Antimycobacterial and antifungal isosters of salicylamides.

A set of 40 derivatives of 3-hydroxypicolinic acid and 2-sulfanylbenzoic acid, isosteric to salicylanilides was synthesized. The compounds were evaluated for in vitro activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium, Candida albicans, Candida tropicalis, Candida krusei, Candida glabrata, Trichosporon beigelii, Aspergillus fumigatus, Absidia corymbifera, Trichophyton mentagrophytes and Microsporum gypseum. Structure-activity relationships of antimycobacterial activity and antifungal activity against T. mentagrophytes and M. gypseum were analyzed by the Free-Wilson method. An increase in antimycobacterial activity was observed only for the sulfanylbenzoic acid derivatives, especially those with the benzyl moiety. The antifungal activity was not significant.

Anti-Bacterial Agents↗

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

Heterocyclic benzazole derivatives with antimycobacterial in vitro activity.

The series of 2-benzylsulfanyl derivatives of benzoxazole and benzothiazole were synthesized, evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis and non-tuberculous mycobacteria, and the activity expressed as the minimum inhibitory concentration (MIC) in micromol/L. The substances bearing two nitro groups (4e, 4f, 5e, 5f) or a thioamide group (4i, 4j, 5i, 5j) exhibited appreciable activity particularly against non-tuberculous strains. The most active compounds were subjected to the toxicity assay and were evaluated as moderately cytotoxic.

Anti-Bacterial Agents↗

PubMed2002

New benzimidazole derivatives as antimycobacterial agents.

A set of 2-alkylsulfanyl derivatives of 5-methylbenzimidazole was synthesized and evaluated for antimycobacterial activity. The structures of the compounds were confirmed by 1H NMR and IR data, and their purity by elemental analysis. Antimycobacterial activities against Mycobacterium tuberculosis and nontuberculous mycobacteria were expressed as the minimum inhibitory concentration. The substances exhibited significant antimycobacterial activity, in particular against both strains of Mycobacterium kansasii. The effect of the most active compound in the set, 3,5-dinitro derivative 3t, exceeded that of the standard isoniazide against M. kansasii and Mycobacterium avium.

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↗

PubMed2002

Synthesis and preliminary evaluation of benzimidazole derivatives as antimicrobial agents.

A series of 2-alkylsulphanylbenzimidazoles was synthesised and the compounds were evaluated for their in vitro antimicrobial activity. The structures of the compounds were confirmed by 1H-NMR and IR data, and their purity by elemental analysis. Antimycobacterial activities against Mycobacterium tuberculosis and non-tuberculous mycobacteria as well as antifungal activities against Candida albicans, Candida tropicalis, Candida krusei, Candida glabrata, Trichosporon beigelii, Trichophyton mentagrophytes and Aspergillus fumigatus were expressed as the corresponding MIC values. The substances exhibited appreciable antimycobacterial activity, in particular, against non-tuberculous mycobacteria. The activity of the most active compound in the set, 3,5-dinitro derivative 4t, exceeded that of the standard isoniazide against M. kansasii and M. avium. The antifungal activities of the compounds were relatively low. A weak antifungal effect was observed against the dermatophyte Trichophyton mentagrophytes. None of the compounds showed significant inhibitory activity against yeasts.

Anti-Bacterial Agents↗