[Azabischalcones--a new class of potential antitubercular agents]. / Azabischalkony--nová trída potenciálních antituberkulotik.

A series of substituted azabischalcones Ia-Ip, monochalcone II and dihydroxyderivative III has been prepared and examined for their in vitro activity against Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium avium, Mycobacterium fortuitum as well as INH-resistant strains. Several compounds under study have the same activity as INH and greater than PAS, Contebene, Ethionamide. The results are summarized in Table 1. In the case of compound Ie, its in vivo activity was studied against M. tuberculosis as well (see Table 2). The toxicity of compounds under study is very low--2000 mg/kg/mouse.

[Relation between chemical structure and antimycobacterial activity against atypical strains. XIII. Thiosalicylanilides]. / Vztahy mezi chemickou strukturou látek a jejich antimykobakteriální aktivitou vuci atypickým kmenum XIII. Thiosalicylanilidy.

On the basis of a preliminary study of antimycobacterial activity of thiobenzanilides a series of eight thiosalicylanilides have been prepared. Synthetized compounds have been examined in vitro against Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium avium and Mycobacterium fortuitum. All compounds have been found very active. The values of minimal inhibitory concentrations are summarized in Table 1. 3',4'-Salicylanilide was selected for the following research. The compound have been found inactive in vivo (on experimental murine tuberculosis).

Antimycobacterial activity of 3'- and 4'-fluorothiobenzanilides.

On the basis of a preliminary study of the antimycobacterial activity of thiobenzanilides, a group of 3'-fluoro- and 4'-fluorothiobenzanilides has been synthesized and tested against Mycobacterium tuberculosis, M. kansasii, M. avium and M. fortuitum. The results of this study demonstrate that electron withdrawing groups increase the activity of thiobenzanilides and fluoro benzothioanilides against atypical strains which is higher then that of INH.

Synthesis and antimycobacterial activity of some new 3-heterocyclic substituted chromones.

The aldol synthesis of benzimidazole, benzothiazole and benzothiazolium salt derivatives of chromones is described. The structures of the compounds have been proved by elemental analysis and 1H NMR spectra. The antimycobacterial activity of some of the prepared compounds have been tested in vitro against Mycobacterium tuberculosis (H37Rv) and Mycobacterium fortuitum (1021).

Research on antifungal and antimycobacterial agents. Synthesis and activity of 4-alkylthiopyridine-2-carbothioamides.

A series of 4-alkylthiopyridine-2-carbothioamides have been prepared and evaluated in vitro for antimicrobial activity. Chemical structures have been demonstrated by IR and 1H NMR data and by elemental analysis. The antimycobacterial activity of these compounds against Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium avium, and Mycobacterium fortuitum, and the antifungal activity against Candida albicans, Candida tropicalis, Candida krusei, Candida glabrata, Trichosporon beigelii, Trichophyton mentagrophytes, Aspergillus fumigatus, and Absidia corymbifera were determined by the MIC values. Compounds 3 exhibit good antimycobacterial activity compared to isoniazide. A moderate antifungal activity was observed against T. mentagrophytes. Activity is influenced by hydrophobicity of the alkyl group.

Chromonyl-aminosalicylic acid derivatives as possible antimycobacterial agents.

N-(2H,3H,4H-4-oxo-6-R1-2-R2O-benzopyran-3-ylidenmethyl) derivatives and imino derivatives of 3-, 4-, 5-aminosalicylic acids were prepared. It was found that some of the synthesized derivatives of 4-aminosalicylic acid are as effective against typical and atypical strains of mycobacteria as isoniazid (INH). Interesting activity of some derivatives against yeast was also found.

[Antitubercular agents. LIV. 3-Alkyl(or -alkyl) thio-2,5-pyrazindicarboxamides]. / Antituberkulotika. LIV. 3-Alkyl(resp.aryl)thio-2,5-pyrazindikarboxamidy.

From 5-cyano-3-chloro-2-pyrazinecarboxamide) (II) hydrolysis in acid medium) yielded 3-chloro-2,5-pyrazinedicarboxamide (III), which in a reaction with sodium hydrogensulfide in dimethyl-formamide) yielded 3-mercapto-2,5-pyrazinedicarboxamide (IV). This compound through condensations with alkyl- and arylhalogenides in triethylamine) yielded 3-alkyl(or aryl) thio-2,5-pyrazinedicarboxamides of type I. The structure of compounds was confirmed by elemental analysis, IR and 1H NMR spectra. A microbiological evaluation was carried out; the antituberculous effect of these compounds is not higher than that of pyrazinamide.

[Relation between the chemical structure of substances and their antimicrobial action against atypical strains. II. 6-acycloamido-2-alkylthiobenzothiazoles, quantitative relation to their effectiveness spectrum]. / Vztahy mezi chemickou strukturou látek a jejich antimykobakteriální aktivitou vuci atypickým kmenum. II. 6-acylamido-2-alkylthiobenzothiazoly, kvantitativní vztahy ke spektru úcinku.

Forty-six 6-acylamido-2-alkylthiobenzothiazoles were tested in vitro for antimicrobial activity towards Mycobacterium avium. The values of logarithms of the minimal inhibitory concentrations (log MIC) are shown in Table 1. The relationships between chemical structure and the activity under study were studied by the Free-Wilson method. The results, contributions of the substituents in positions 2 and 6 and the contribution of the common benzothiazole part (marked C) to the activity (delta log MIC) are shown in Table 2. Regression equation correlating the contributions and fragmental hydrophobic constants (f) belonging to the unbranched alkyl groups bound to the sulphur atom in position 2 (see Table 2) are not statistically significant (equation 8). The initial data for a complex analysis of the structure--antimycobacterial activity relationships with regard to the equipotency of the activity towards the species mentioned below form the values of log MIC and the derived values delta log MIC towards Mycobacterium tuberculosis, M. kansasii (see ref.9) and M. avium (see above). According to it, to each drug, each molecular fragment, the vector of activities A is attributed (equation 1), or the vector of contributions a (equation 7). Complex analysis is based on the idea of comparison (similarity) of the drug under study with an "ideal" drug, which possesses the required profile of activities. The vector uk corresponding to it is given for the above-considered case (of wide spectrum) by relation 5, for the case of selectivity with regard to the 1st activity by relation 4. The fundamental concepts of vector algebra, particularly the scalar product of vectors (A, uk) (relation 3) are used as the criteria of decision.(ABSTRACT TRUNCATED AT 250 WORDS)

[Antitubercular agents. 45. Antimycobacterial thiohydrazide]. / Antituberkulotika. 45. Mitteilung: Antimykobakterielle Thiohydrazide.

The present paper investigates the activity of thiohydrazides containing a structural fragment of oxalic acid against Mycobacterium tuberculosis and Mycobacterium kansasii. The drugs included heterocyclic compounds as well. All compounds under study show medium activity. The minimal inhibition concentrations against Mycobacterium kansasii are approximately 3 times higher than against Mycobacterium tuberculosis. The most effective aromatic compounds have the RM values (silica gel impregnated with silicon oil-water) in the interval of 2.2-2.6.

[Relation between chemical structure, antitubercular activity and hepatotoxicity of 2-alkylthio-6-benzamidobenzothiazoles]. / Beziehungen zwischen chemischer Struktur, antituberkulotischer Aktivität und Hepatotoxizität von 2-Alkylthio-6-benzamidobenzothiazolen.

The paper investigates the relationships between hydrophobic parameters and antituberculotic activity of 2-alkylthio-6-benzamidobenzothiazoles, tested on INH-resistant strain of Mycobacterium tuberculosis. In the group of compounds with linear alkyl substituents in position 2, the tuberculostatic effect is increasing with decrease of lipophility of alkyls. Branching of the alkyls strongly increases the activity. The hepatotoxicity of compounds under study was investigated by means of the activity of serum aminotransferases (ALT, AST) in Wistar type rats. The hepatotoxicity of compounds seemed to be smaller than that of the thiobenzamides.

[The relation between antimycobacterial activity and complex formation of various compounds]. / Zusammenhang zwischen antimykobakterieller Aktivität und Komplexvermögen einiger Stoffe.

Analytic agents were tested from the point of view of their antimycobacterial effect. It was found, that substances forming complexes with Cu-ions, namely dithiocarbamates and their oxidation products, show very high antimycobacterial activity. Small stability of the dithiocarbamates in acidic medium leads to the tests, the aim of which was to replace these substances with chemically stable, but antimycobacterially active compounds. Dibenzoyldisulfide was found as one of these substances.