Biomedical subjects
Publications and source records attributed to K Waisser.
The antimycobacterial activity of 2,3-dianilinoquinoxaline derivatives was studied and the substances were found to be mostly wide-spectrum antimycobacterial agents. Replacement of one nitrogen atom in the heterocycle for oxygen or sulfur was usually accompanied by loss of activity. The model structure for the study was the wide-spectrum antimycobacterial drug clofazimine.
The present review paper is the first collected communication about biological activity of benzanilides. The substances of the above-mentioned structures show a number of activities (antibacterial, ref. 1-22; antituberculous, ref. 23-25; antimycotic, ref. 26-95; antiviral, ref. 96-98, antiprotozoan, ref. 97; anthelmintic, ref. 37, 99-100; insecticidal, ref. 31, 37, 101-104; herbicidal, ref. 106-130, antitumour, ref. 131-137; immunosuppressive, ref. 134, 138; hypnotic, ref. 140; anticonvulsive, ref. 141-151, anti-inflammatory, ref. 152; local-anaesthetic, ref. 155-156; antiarrhythmic, ref. 155, 158; vasodilating, ref. 159; antiulcerative, ref. 160; anti-androgenic, ref. 161; hypoglycemic ref. 162). Only very few of them have been hitherto introduced into practice. Papers investigating biological activity of benzanilides can be encountered also at present.
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.
The review paper is the first collected communication about the biological activity of 3-aryl-2H,4H-benz(e)(1,3)oxazine-2,4-diones and thiosalicylanilides. The substances of the above mentioned structures show a number of biological activities (antibacterial, antituberculous, antimycotic, anthelmintic, molluscocidal, neuroleptic, analgesic and anti-inflammatory) which can be modelled by structural changes. Only very few of them have been hitherto introduced into practice as anthelmintic agents, or agents with a special purpose (destroying the sea lamprey in Canadian lakes). In the group of 3-aryl-2H,3H-benz(e)(1,3)-oxazine-2,4-diones, i.e. substances developed from salicylanilides by the action of alkyl-chloroformiates, antibacterial activity is reported in refs. 3-12, antituberculous activity in refs. 13, 14, antimycotic activity in refs. 5, 6, 9, 12, 15, 16, anthelmintic activity in refs. 6,917-20, molluscocidal activity in refs. 6, 21, analgesic and anti-inflammatory activity in refs. 22-24, herbicidal activity in refs. 25, 26, allergenic activity in ref. 27. In the group of salicylanilides, antibacterial activity is reported in refs. 28-37, antimycotic activity in refs. 28-36, antiprotozoal activity in ref. 35, anthelmintic activity in refs. 28-40, 49, molluscocidal activity in refs. 7, 28-36. The present paper furthermore sums up the papers concerned with the toxicities of the above-mentioned agents. Though the peak of research of the groups of the above-mentioned structure was in the 1960s and 1970s, papers investigating their biological activity can be encountered also at present.
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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.
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)
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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.
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.
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