Synthesis, antimicrobial testing and QSAR study of new 2-phenylethenylbenzothiazolium salts substituted by cyclic amines.

A series of new 2-phenylethenylbenzothiazolium salts substituted by cyclic amines has been prepared by the condensation of 2-methyl benzothiazolium bromide with substituted benzaldehydes. The nucleophilic substitution of 4-fluorobenzaldehyde with appropriate cyclic amines has been used to obtain the starting benzaldehydes. The compounds with saturated cycloamino substituents have shown enhanced activity against Euglena and some derivatives with piperazine substituent were active against Gram positive bacteria.

Activity of some 3-formylchromone derivatives on the induction of chloroplast-free mutants in Euglena gracilis.

The hereditary bleaching test on Euglena gracilis was used for detecting extranuclear mutations. The highest bleaching activity (induction of the chloroplast-free mutants) was shown by the 6-R-3-formylchromones. On the other hand, bleaching-inactive 6-R-3-formylchromone acylhydrazones (derived from gallic and salicylic acids), added at sufficient concentrations in the case of chloroplast mutagenesis in E. gracilis, act as a potent antimutagen. This effect appeared to be a unique feature of chromone derivatives, but was dependent on the type of mutagen. These substances were very effective against the bleaching activity of acridine orange, and were less effective against N-methyl-N'-nitro-N-nitrosoguanidine. The genotoxic effects of these mutagens was reduced, especially during the first stages of induction of this specific cytoplasmic mutation. The experimental study of mutagenicity and antimutagenicty of 3-formylchromone hydrazones was reinforced by data obtained by the semi-empirical AM1 method and lipophilicity values.

Synthesis and antimicrobial activity of new 2-phenylethynylbenzothiazoles and related salts.

New 2-phenylethynylbenzothiazoles were synthesized by coupling reaction between 2-iodobenzothiazole and substituted phenylacetylenes under palladium catalysis. The modified Wittig reaction was used to prepare the substituted phenylacetylenes from corresponding benzaldehydes. 2-Phenylethynylbenzothiazoles were next quarternized with trimethyloxonium tetrafluoroborate to 3-methylbenzothiazolium salts. Antimicrobial in vitro activities were determined for all new compounds.

Synthesis, antimicrobial activity and bleaching effect of some reaction products of 4-oxo-4H-benzopyran-3-carboxaldehydes with aminobenzothiazoles and hydrazides.

The synthesis of the biologically active novel systems derived from reaction of 3-formylchromones with three types of amino derivatives, 6-R2-2-aminobenzothiazoles, 6-amino-2-R3-thiobenzothiazoles and hydrazide derivatives (derived from cyanoacetic, isonicotine, salicylic and gallic acids) was carried out. The structures of the prepared compounds have been proved by elemental analysis, 1H NMR and IR spectra. Antimicrobial activity was studied against the following microorganisms--bacteria G+ (Staphylococcus aureus 29/58, Bacillus subtilis 18/66), G- (Escherichia coli 326/71, Pseudomonas aeruginosa); yeasts: Candida albicans, Saccharomyces cerevisiae; moulds: Microsporum gypseum, Aspergillus niger, Scopulariopsis brevicaulis; and against typical and atypical mycobacteria: Mycobacterium tuberculosis (H37Rv), Mycobacterium kansasii (PFG 8), Mycobacterium avium (My 80/72), Mycobacterium fortuitum (1021). The hereditary bleaching effect on the plastid system of Euglena gracilis, a unique phenomenon of the biological activity of chromone derivatives, is reported. The bleaching test on E. gracilis is used for detecting extranuclear mutations.

Euglena gracilis as an eukaryotic test organism for detecting mutagens and antimutagens.

The unicellular flagellate Euglena gracilis was used in order to assess the inhibition of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and N-methyl-N-nitrosourea (MNU) mutagenicities, which induce white mutants due to the irreversible loss of chloroplasts. All tested compounds, including o-aminobenzoic acid and p-aminobenzoic acid, salicylic acid, acetylsalicylic acid, sodium salicylate and p-aminosalicylic acid, were not mutagenic per se and inhibited MNNG mutagenicity by at least 50%. The last two compounds inhibited by at least 50% also MNU mutagenicity.

Qsar study of the toxicity of benzothiazolium salts against Euglena gracilis: the Free-Wilson approach.

The Free-Wilson QSAR model in the Fujita-Ban modification was used to calculate the quantitative substituent activity contributions to the toxicity against Euglena gracilis in a series of 91 benzothiazolium salts. An important increase of activity was found for R1 = styryl or SCH2C6H5 group and for R2 = propargyl or allyl group. The substituents on benzene ring also enhance the activity. The possible relations between structure of active groups and their electronic or physicochemical properties are discussed. By using the calculated values it is possible to predict toxicity for 1300 compounds. New compounds with assumed high or low toxicity are predicted.

Antimutagenicity in Euglena gracilis.

The genotoxic effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and furadantine (Fu) was significantly decreased by standard antimutagens (ascorbic acid, alpha-tocopherol, chlorophyllin and sodium selenite) in the unicellular flagellate Euglena gracilis. The effects of these compounds were verified also by a bacterial test in which three strains of Salmonella typhimurium, TA97, TA100, and TA102, were used. The above compounds were antimutagenic in strains of bacteria used, except for chlorophyllin which had no effect on strain TA102.

Benzothiazolium salts--relationships between their structure, toxicity and effect on the plastid system of Euglena gracilis.

The effects of 41 benzothiazolium salts on Euglena gracilis were characterized with regard to the influence on growth and on chlorophyll synthesis, and to their ability to induce permanent loss of chloroplasts. Some salts induced white mutants of E. gracilis (the first benzothiazole derivatives with this activity). The relationship between the biological effect and chemical structure was confirmed and expressed quantitatively by means of Free - Wilson and Fujita - Ban analysis.

Effect of some benzthiazol derivatives on Euglena gracilis.

6-Substituted derivatives of 2-benzthiazolthiol and allyl (2-benzthiazolylthio)acetate exhibit, after an exposure to light, and inhibitory action on the division of dark-depigmented Euglena cells, as well as the synthesis of chlorophyll. These substances also have a marked inhibitory effect on the devlopment of plastids in nondividing cells maintained under resting conditions. No induction of heterotrophic plastid--free mutants was found under growth or resting conditions.

Antimicrobial effects of some benzthiazol derivatives.

Substitution with NO2, Cl, Br and I into position 6 of 2-benzthiazolthiol derivatives increased their antimicrobial efficiency while the SH group is preserved. This increase affected both G+ and G--bacteria, mycobacteria and some fungi. The degree of efficiency of the benzthiazol derivatives is also influenced by the substituent in position 2.