Testing against Mycobacterium

Several organotin complexes of the oxicams and other NSAIDs have been tested against Mycobacterium tuberculosis. The complexes n-Bu2Sn(84 ), w-Bu2Sn(87a ) (90) ,... 

Quinolizidine derivatives with a more or less extended and planar aromatic moiety displayed antimicrobial activity [256]. Similar compounds were prepared for testing against Mycobacterium tuberculosis, due to the growing concern for the upsurge of new cases of tuberculosis and of non-tuberculous mycobacterioses in the western world since 1986. Several quinolizidines (Q) bearing different aryl nuclei substituents (which changed both the electronic distribution and the lipophilic-hydrophilic balance of the molecule) were synthesised. Six of these synthesised compounds (Q1-Q6), Fig. (42), were highly active and it is reasonable to state that... 

Compound 223f exhibited a significant activity against Staphylococcus aureus, and 223g revealed the best product tested against Mycobacterium fortuitum with a minimum inhibitory concentration (MIC) value of 32 pg/mL. 

The same PEC system but loaded with streptomycin, gentamicin, or tobramycin was recently reported by Popescu and coworkers [137] and tested against mycobacterium tuberculosis in a mouse model. Particle sizes in the nanometer range were obtained, and release studies showed residual drug amounts of > 60% in the nanoparticle interior at low acidic pH after 6 h. Oral administration of streptomycin-loaded particles reduced bacilli growth by a factor of 10, similarly effective to subcutaneously injected aqueous streptomycin solution at a concentration of 0.1 mg/mL. 

Some of the N-alkylated narceine amides and imides were tested for antibacterial effectiveness and showed activity of medium potency against Mycobacterium tuberculosis H37 Rv. Their antimycotic activity was also of medium strength. Coccidiostatic screening showed some effectiveness (100). 

Labdanes of the series of gomojosidae, isolated from the leaves of Viburnum suspensum (Caprifoliaceae) exhibited antibacterial activity against E.coli, Aeromonas salmonishida and B. subtillis [102]. Cryptotrienolic and isocupressic acid isolated from the bark of Juniperus procera were found to exhibit weak antibacterial activity when tested against B. subtillis, S. aureus, Str. durans, E. faecilis, and Mycobacterium... 

Materials. The silver composition of the present invention comprised 10 ppm silver in water. The silver composition was evaluated employing a liquid to liquid matrix against Mycobacterium bovis BCG (TMC 1028). This organism causes tuberculosis in animals and can cause tuberculosis in humans. It is used as a stand-in for M. tuberculosis, the major cause of human tuberculosis, as tests have shown it to have a similar susceptibility to M. tuberculosis. The test organism was exposed to the silver composition in duplicate at four exposure times and quantified using membrane filtration. 

The compounds prepared were tested for their inhibitory activity against Mycobacterium tuberculosis glutamine synthetase (MtGS), an enzyme that plays a key role in mycobacterial cell-wall biosynthesis and nitrogen metabolism. Compound... 

Thus, Bhaskar et al. developed a novel US-enhanced latex agglomeration test for the detection of serum antibodies against Mycobacterium tuberculosis. The use of US enabled the detection of low levels of antibodies in serum by increasing the sensitivity of the test. The rate of particle-particle collisions under an oscillator frequency of 100 kHz was raised to such an extent that the sensitivity for samples diluted up to 20 times exhibited agglutination, which was visible to the naked eye [76]. Figure 5.6 clearly shows the advantage in using US for this purpose. 

The antitubercular activity of 2-carbamoylpyrazine and biological activity of pyrazines generally has been mentioned in Section 1.4. Certain pyrimidinyl derivatives of 2-carbamoylpyrazine have been shown to have lower toxicity and rather greater in vitro activity against Mycobacterium tuberculosis than 2-carbamoylpyrazine (1388), and the antitubercular activity of some extranuclear )V-substituted carbamoylpyrazines also showed a higher activity than 2-carbamoylpyrazine (1201). When tested on mice in vivo, 2-carbamoyl-5-methoxypyrazine and 2-hydrazino-carbonylpyrazine had less antitubercular activity than did 2-carbamoylpyrazine (1098) the antitubercular activities in a series of hydrazinocarbonyl-, carbamoyl-, and thiocarbamoylpyrazines have been examined and compared (1399). 

In a recent study, with S. multicaulis, four of the new compounds (29-32) showed structural resemblence to tanshinone-type compounds. Therefore, they and the other new compounds (33-34 ) isolated from the same plant, were tested against bacterial strains (Table 28). All the compounds from this plant were also tested in Mycobacterium tuberculosis H37Rv test system. Their antituberculous activity was established according to broth microdilution method . When the MIC results were... 

Members of the CC class of chemokines are involved in the recruitment of leukocytes in both the innate and acquired phases of the immune response against Mycobacterium. In addition, since the successful clearing of mycobacteria by the host is critically dependent on the development of a T-1 phenotype-acquired immune response, several studies in the literature have tested the components of an effective Th-1 response by examining the host response to mycobacteria or mycobacterial antigens. 

A thorough literature search for these two compounds resulted in the following Compound A (R = t-Bu, R = W-methylpiperazin-l-yl) was synthesized and published already in 1987/1988 in a patent application (US 916757, EP 0266576) as an antibacterial agent. It shows activity against several bacteria, but seemingly was not tested with Mycobacterium fortuitum. 

The synthesized compounds were tested for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB). Compound 268a showed the most promising result with an MIC (minimum inhibitory concentration) value of 1.98 pM against MTB. It was also up to 26 times more potent than ethambutol and pyrazinamide, the standard first line TB drugs. 

A glycoresin-containing crude extract of the leaves/stems from Ipomoea leptophylla had shown moderate activity (92% inhibition at an initial test concentration of 150 J,g/ml) against Mycobacterium tuberculosis, the pathogen causing tuberculosis. Bioassay-guided fractionation led to the isolation of leptophyllin A which appeared to be the major active component (Barnes et al. 2003). 

Tuberculocidal Test. The tubercle bacillus is resistant to disinfectants because the cells are protected with a waxy coating that is not readily penetrated. The tuberculocidal test is a use dilution practical type test that employs porcelain cylinders. The bacteria are different from those in the use dilution method (Table 10), the incubation time is longer, and the details of the procedure are different. For example, in the tuberculocidal test the test is divided into two parts, a presumptive test and a confirmatory test. The former employs Mycobacterium smegmatis and the latter employs Mycobacterium bovis (BCG). For the presumptive test the incubation time is 12 days, as against 48 hours for other bacteria used in the use-dilution method. For the confirmatory test the incubation time is 60 days, with an additional 30 days in case there is no growth. As shown in Table 10, the concentrations of the phenol standard are higher than used with other bacteria. 

Twenty-five dibenzothiophenes, composed mainly of amino and acetamidodibenzothiophenes and their sulfoxides and sulfones, have been tested for antibacterial activity against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. Activity was found against the latter with 2- and 3-aminodibenzothiophene in synthetic culture media, but the effect was reversed by the addition of serum. " ... 

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