Mycobacterium tuberculosis activity against

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. " ... 

In 2005, Franzblau et al. isolated micromeline (100) from the stem bark of M. hirsutum (103). This alkaloid exhibited in vitro anti-TB activity against the H37RV strain of Mycobacterium tuberculosis and against the Erdman strain of M. tuberculosis... 

Sudol uses fractions of coal tar rich in xylenols and ethylphenols. It is much more active and less corrosive than lysol, and remains more active in the presence of organic matter. The phenol coefficients of sudol against Mycobacterium tuberculosis, Staphylococcus aureus, and Pseudomonas aeruginosa are 6.3, 6, and 4, respectively. It also is slowly sporicidal (97). 

The thiophene analog of chloramphenicol (255) has been synthesized,as also have been similar structures. The antibacterial activity of all was much lower than that of the natural antibiotic. The thioamide of 2-thenoic acid has been prepared in a study of potential antitubercular compounds. It did not surpass thioisonico-tinamide in antitubercular activity. The thiosemicarbazones of thio-phenealdehydes and ketones (cf. Section VII,D) show high activity against Mycobacterium tuberculosis, but are very toxic. The thiosemi-carbazone of 4-(2-thienyl)-3-buten-2-one has been reported to be capable of completely inhibiting the in vitro growth of M. tuberculosis even in relatively low concentrations. ... 

The antimicrobial activity of thiosemicarbazones against Mycobacterium tuberculosis in vitro was first reported by Domagk et al. [28] and later confirmed in vivo [29]. Screening revealed that only certain substituted be-nzaldehyde and heterocyclic thiosemicarbazones possess antitubercular activity [30-32]. The most widely used is p-acetamidobenzaldehyde thiosemicarbazone (trivial name = thiacetazone), 1. 

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). 

The most active aminoglycoside against Mycobacterium tuberculosis is... 

Substituted, particularly hydroxyphenylmethyl- or hydroxyalkyl substituted, indolizines have shown activity against Mycobacterium tuberculosis <2006MI26>. 3-Substituted indolizine-l-carbonitrile derivatives displayed activity against MPtpA/MPtpB phosphatases which are involved in infectious diseases <2006BMCL59>. 

Rifampicin is highly active against Mycobacterium tuberculosis. Among atypical mycobacteria, it is active against Mycobacterium kansasii, Mycobacterium marinum, and most types of Mycobacterium scrofulaceum and Mycobacterium xenopi. Sensitivity of other mycobacteria varies. Rifampicin also exhibits activity against Mycobacterium leprae. 

Pharmacology Isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels, isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. 

Pharmacology Rifampin inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase, but does not inhibit the mammalian enzyme. Cross-resistance has only been shown with other rifamycins. Rifampin at therapeutic levels has demonstrated bactericidal activity against intracellular and extracellular Mycobacterium tuberculosis organisms. Pharmacokinetics ... 

Metabolism Rifampin is metabolized in the liver by deacetylation the metabolite is still active against Mycobacterium tuberculosis. About 40% is excreted in bile and undergoes enterohepatic circulation however, the deacetylated metabolite is poorly absorbed. The half-life is approximately 3 hours after a 600 mg oral dose, up to 5.1 after a 900 mg oral dose. With repeated administration, the half-life decreases and averages approximately 2 to 3 hours. 

In 1991, McChesney and El-Feraly described the isolation and structural elucidation of 3-formyl-6-methoxycarbazole (97) from the roots of C. lansium (23). The roots of this ornamental tree are used in traditional medicine in Taiwan to treat bronchitis and malaria (23). In 2005, Franzblau et al. isolated the same natural product from the stem bark of Micromelum hirsutum (103). They reported that 3-formyl-6-methoxycarbazole (97) shows in vitro anti-TB activity against the H37RV strain of Mycobacterium tuberculosis. 

In 2003, Sunthitikawinsakul et al. described the anti-mycobacterial activity of various 3-methylcarbazole derivatives, including 3-formylcarbazole (3), methyl carbazole-3-carboxylate (4) (see Scheme 2.2), clausine K (clauszoline-J) (51) (see Scheme 2.11), and 7-methoxymukonal (68) (see Scheme 2.14) against Mycobacterium tuberculosis H37Ra. Except for clausine K (clauszoline-J) (51), all of these alkaloids also showed anti-fungal activity against Candida albicans (442). In 2005, Eranzblau et al. reported the in vitro anti-TB activity of various carbazole derivatives such as 3-formylcarbazole (3), methyl carbazole-3-carboxylate (4) (see Scheme 2.2), lansine... 

Ansamycins, like the macrolides, are synthesized by condensation of a number of acetate and propionate units. These antibiotics, which are produced by several genera of the Actinomy-cetales, display a characteristic core aromatic ring structure. Amongst the best-known family members are the rifamycins, which are particularly active against Gram-positive bacteria and mycobacteria. They have been used, for example, in the treatment of Mycobacterium tuberculosis. 

Amikacin and kanamycin (see Chapter 46) have been used in the treatment of tuberculosis. Amikacin is very active against several mycobacterium species however, it is expensive and has significant toxicity. It is considered in the treatment of MDR tuberculosis after streptomycin and capreomycin. An additional use of amikacin is in the treatment of disseminated MAC in AIDS patients. There is no cross-resistance between streptomycin and other aminoglycosides most M. tuberculosis strains that are resistant to streptomycin are... 

Clofazimine is given to treat sulfone-resistant leprosy or to patients who are intolerant to sulfones. It also exerts an antiinflammatory effect and prevents erythema nodosum leprosum, which can interrupt treatment with dapsone. This is a major advantage of clofazimine over other antileprosy drugs. Ulcerative lesions caused by Mycobacterium ulcerans respond well to clofazimine. It also has some activity against M. tuberculosis and can be used as last resort therapy for the treatment of MDR tuberculosis. 

Fitzpatrick, F. K. Plant substances active against Mycobacterium tuberculosis. Antibiot Chemother 1954 4 528. Saha, J. C., E. C. Savini, and S. Kasinathan. Ecbolic properties of Indian medicinal plants. Part I. Indian J Med Res 1961 49 130-151. 

DC026 Gottshall, R. Y., E. H. Lucas, A. Lickfeldt, and ]. M. Roberts. The occurrence of antibacterial substances active against Mycobacterium tuberculosis in seed plants. J Clin Invest 1949 28 920-923. 

It is the most active drug used in the treatment of tuberculosis. It is a hydrazide of isonicotinic acid. It is a bactericidal drug, effective against Mycobacterium tuberculosis and ineffective against atypical mycobacteria. 

It is chemically related to nicotinamide and thiosemicarbazone. It is bactericidal. It is effective against Mycobacterium tuberculosis resistant to INH and streptomycin. It is converted to pyrazinoic acid (active... 

It is a peptide protein synthesis inhibitor antibiotic isolated from Streptomyces capreolus. It is second line antimycobacterial drug which exhibits activity against human strains of Mycobacterium tuberculosis. 

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