Studies on pyrazine derivatives--XXXIV. Synthesis and tuberculostatic activity of alpha-oxo ketene dithioacetals pyrazine derivatives.

The alpha-oxo ketene dithioacetalic derivatives (2a-e) were obtained by the reaction of 2-acetylpyrazine (1) with CS2 and appropriate mono- or dihalogeno-compound. An action of the primary amines and diamines upon 3,3-di(methylsulphanyl)-1-(2-pyrazinyl)-2-propen-1-one (2a) yielded 3-(alkylamino)-3-(methylsulphanyl)-1-(2-pyrazinyl)-2-propen-1-on e (3a-g), 1-(2-pyrazinyl)-2-tetrahydro-1H-2-imidazolyliden-1-ethanone (3h) and the 2-hexahydro-2-pyrimidinyliden-1-(2-pyrazinyl)-1-ethanone derivatives (3i-j), respectively. Tuberculostatic activity of the studied compounds was found to be low except the compound 2b (MIC 192-62 micrograms/cm3; MIC 210-31 micrograms/cm3).

Synthesis and some reactions of 2-acetylimidazo[4,5-b]pyridine. Antituberculotic activity of the obtained compounds.

2-Acetylimidazo[4,5-b]pyridine was prepared and its reactions with some aromatic amines and sulfur (Willgerodt-Kindler reaction), some aromatic aldehydes, some carboxylic acid hydrazides as well as thiourea were investigated. New imidazo[4,5-b]pyridine derivatives with different substituents in 2-position (N-arylthioamides, imines, alpha, beta-unsaturated ketones, hydrazido-hydrazones and aminothiazole) were obtained. Most of the synthesized compounds were tested in vitro for their antituberculotic activity.

Studies on pyrazine derivatives. XXXIII. Synthesis and tuberculostatic activity of 1-[1-(2-pyrazinyl)-ethyl]-4-N-substituted thiosemicarbazide derivatives.

Hydrogenation of 4-N-substituted thiosemicarbazonic acid acetylpyrazine derivatives with NaBH4 in dry ethanol led to seventeen new compounds. The in vitro tuberculostatic activity investigations of the 15 synthesized compound were carried out. MIC few of i.v. compounds were lower than 32 micrograms/cm3.

Studies on pyrazine derivatives. XXXII. Synthesis and tuberculostatic activity of acetylpyrazine thiosemicarbazone derivatives.

Syntheses of 4-N-substituted thiosemicarbazoic acetylpyrazine derivatives have been described. The in vitro microbiological investigations of the 25 synthesized compound were carried out.

Some reactions of 2-cyanomethylimidazo[4,5-b]pyridine with isothiocyanates. Antituberculotic activity of the obtained compounds.

Some reactions of 2-cyanomethylimidazo[4,5-b]pyridine with isothiocyanates were carried out. New derivatives of imidazo[4,5-b]pyridine with different substituents in 2-position and derivatives of the new thiazolo-pyrido-imidazo-pyrimidine ring system were synthesized. Most of the obtained compounds were tested in vitro for their antituberculotic activity.

Cellular reaction to Mycobacterium avium complex (MAC) clinical isolates differing in hemolytic activity and virulence for C57BL/6 mice.

In this study we showed that Mycobacterium avium complex (MAC) clinical isolates differed by the expression of hemolytic activity. Two hemolytic MAC strains were less susceptible to the mycobactericidal effect of murine macrophages than two unhemolytic MAC isolates. In vivo, hemolytic MAC bacilli survived in the spleens of infected mice for a longer time than unhemolytic MAC strains. This suggested a role of hemolysins in the virulence of MAC strains. There was no difference in the cytotoxicity of T cells from mice immunized with M. bovis BCG towards macrophages infected in vitro with MAC strains expressing or not expressing hemolytic activity.

Haemolytic activity of Mycobacterium spp.

Haemolytic activity of clinical isolates of Mycobacterium bacilli (98) was determined by the method of King et al., 1993. During 3-h incubation, all M. tuberculosis (MTB) isolates (28) and one out of 38 M. avium-intracellulare (MAI) strains, produced a strong contact-dependent haemolysin (CDH). Six MAI strains expressed a weak CDH. One MAI isolate produced a strong and five other MAI strains a weak contact-independent haemolysin (CIH). Two M. bovis BCG strains and 7 M. vaccae strains did not demonstrate haemolytic activity. The persistence of chosen Mycobacterium strains differing by haemolytic activity, in the spleens of infected C57BL/6 mice was examined. Mycobacteria producing a strong CDH (MTB H37Rv, MTB 101/92, MAI 83/93) or CIH (MAI 475/93) survived in the spleens of nonimmunized or M. bovis BCG-immunized mice for longer time than MAI strains expressing weak haemolytic activity or M. bovis BCG vaccine strain.

[Combination of gentamycin and amikacin with rifampicin, ethambutol and isoniazid on selected standard strains of Mycobacterium species in experiments done in vitro and in vivo]. / Skojarzone dzialanie gentamycyny i amikacyny z ryfampicyna etambutolem i hydrazydem kwasu izonikotynowego na dobrane szczepy wzorcowe z rodzaju Mycobacterium w doswiadczeniach in vitro i in vivo.

The authors present results of in-vivo and in-vitro studies of combined effect of gentamycin , amikacin and rifampicin , ethambutol, isoniazide on selected standard strains of Mycobacterium sp. (Myc. H37Rv, Myc. An5, Myc. wells, Myc. kirchberg, Myc. kansasii, Myc. intracellulare, and Myc. fortuitum). In in-vitro studies the synergistic effect of gentamycin and amikacin with the tuberculostatic drugs was demonstrable on all Mycobacterium strains. The weakest effect was seen on Myc. fortuitum colonies. In-vivo studies have also shown this synergistic effect on all studied strains, and a much weaker effect when used in monotherapy. The authors have shown the possibility of using combination of gentamycin and amikacin with RMP, EMB, INH in treating Myc. intracellulare infections.