Disease relevance of Thioacetazon

• No controlled trials have investigated the safety and efficacy of thiacetazone-containing regimens compared with alternative regimens among patients with HIV [1].
• Randomised trial of thiacetazone and rifampicin-containing regimens for pulmonary tuberculosis in HIV-infected Ugandans. The Makerere University-Case Western University Research Collaboration [1].
• Thiacetazone-induced hypersensitivity [2].
• Cutaneous hypersensitivity reactions due to thiacetazone in HIV-1 seropositive patients treated for tuberculosis [3].
• MAIQ (4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone) produced apparent inactivation of HSV-1 ribonucleotide reductase [4].

High impact information on Thioacetazon

• In contrast, MAb 42/6 had minimal effects on cytotoxicity of the ribonucleotide reductase inhibitor, isoquinaldehyde thiosemicarbazone, to either HL60 or KB cells [5].
• Among HIV-positive patients who received treatment for active tuberculosis, thiacetazone has been associated with cutaneous hypersensitivity and recurrent tuberculosis [1].
• As an alternative approach to using P-gp inhibitors, we characterize a thiosemicarbazone derivative (NSC73306) identified in a generic screen as a compound that exploits, rather than suppresses, P-gp function to induce cytotoxicity [6].
• While the ED2 cells showed resistance to 2,3-dihydro-1H-pyrazole-[2,3a]-imidazole/Desferal (6-fold), the ED1 and ED2 cell lines showed less resistance to hydroxyurea, 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone, and the dialdehyde of inosine [7].
• Studies were carried out to determine the effects of preincubation of 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone (MAIQ) with hepatic microsomes on the ability of MAIQ to inhibit CDP reductase activity in vitro [8].

Chemical compound and disease context of Thioacetazon

• In all patients with a cutaneous hypersensitivity reaction ethambutol was substituted for thiacetazone [9].
• 3-HMP and 5-HMP both showed better antitumor activity than their respective parent compounds, 3-hydroxypyridine-2-carboxaldehyde thiosemicarbazone and 5-HP, in mice bearing the L1210 leukemia [10].
• Inhibition of vesicular stomatitis virus by kethoxal bis (thiosemicarbazone) [11].
• Oxidative activation of thiacetazone by the Mycobacterium tuberculosis flavin monooxygenase EtaA and human FMO1 and FMO3 [12].
• Several novel pyrazolin-5-ones prepared by the cyclization of variously substituted thiosemicarbazone derivatives of ethyl formylsuccinate, ethyl acetylsuccinate, and ethyl acetylglutarate were tested for antitubercular activity against Mycobacterium tuberculosis, human type, strain H37Rv, by a tube dilution technique [13].

Biological context of Thioacetazon

• Synthesis and structure-activity relationships of parasiticidal thiosemicarbazone cysteine protease inhibitors against Plasmodium falciparum, Trypanosoma brucei, and Trypanosoma cruzi [14].
• The effects of thiacetazone on human chromosomes are not known [15].
• Chromosome aberrations were significantly increased in the patients treated with INH and thiacetazone as compared with two types of controls: (1) tuberculosis patients before starting the drug treatment and (2) individuals from the general population [15].
• 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) and 3-amino-4-methylpyridine-2-carboxaldehyde thiosemicarbazone (3-AMP) were the most active compounds tested with respect to inhibition of cell growth and ribonucleotide reductase activity [16].
• Among the biodegradable esters examined as potential rivals of thiacetazone, only aspirin competitively inhibited thiacetazone hydrolysis (Ki = 2.1 x 10(-4) M) [17].

Anatomical context of Thioacetazon

• In mice, SRI-224 and thiacetazone had no significant activity against the MAC in livers and spleens, but treatment with SRI-286 resulted in significant reduction of bacterial loads in livers and spleens [18].
• Novel tetranuclear orthometalated complexes of Pd(II) and Pt(II) derived from p-isopropylbenzaldehyde thiosemicarbazone with cytotoxic activity in cis-DDP resistant tumor cell lines. Interaction of these complexes with DNA [19].
• Our results indicate that the increase in volume may be due to the increased rod diameter near the tooth surface, a circumferential winding of rods in the parazone orientation of Hunter-Schreger bands, and the migration of rods from a mid-coronal origin at the dentin surface to a cuspal terminaton at the tooth surface [20].
• Kethoxal bis (thiosemicarbazone) (KTS) inhibited replication of, and plaque formation by, vesicular stomatitis virus (VSV) in chick embryo cells [11].
• HIgh-performance liquid chromatographic determination of thiacetazone in body fluids [21].

Associations of Thioacetazon with other chemical compounds

• In this paper the syntheses of new pyridoxal thiosemicarbazone copper(II) and cobalt(III) complexes with nitroprusside as a counterion and tests on the antileukemic activity of three of these complexes toward human cell lines U937 and CEM are reported [22].
• 2-Formyl-3-hydroxy-4,5-bis(hydroxymethyl)pyridine thiosemicarbazone was synthesized in an attempt to direct the chelating potential of this agent to the active site of the zinc-requiring enzyme pyridoxal phosphokinase [23].
• DESIGN: A cross-sectional study whereby 167 isolates were tested for susceptibility to the anti-tuberculosis drugs commonly used in the country (isoniazid, thiacetazone, rifampicin, streptomycin and ethambutol) [24].
• It is known that metallic complexes of methyl 2-pyridyl ketone thiosemicarbazone (HL1) and p-isopropyl benzaldehyde thiosemicarbazone (HL2) may have potential antitumor activity [25].
• Three new complexes of transition metals as copper, nickel and cobalt with 5-formyluracil thiosemicarbazone (H3ut) have been synthesised and characterised by single-crystal X-ray diffraction [26].

Gene context of Thioacetazon

• Relationships between sensitivity to hydroxyurea and 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone (MAIO) and ribonucleotide reductase RNR2 mRNA levels in strains of Saccharomyces cerevisiae [27].
• Flow cytometry has been used to detect estrogen receptor (ER) in intact cells, using 1-(N)- fluoresceinyl estrone thiosemicarbazone ( 17FE ), a ligand shown to have sufficient affinity and specificity to identify high-affinity receptors [28].
• 0. The Km and Vmax values for the N-deacetylation of thiacetazone are 5.7 x 10(-4) M and 0.123 nmol of p-aminobenzaldehydethiosemicarbazone formed/min/mg cytosolic protein, respectively [17].
• Overexpression of protein disulfide isomerase-like protein in a mouse leukemia L1210 cell line selected for resistance to 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone, a ribonucleotide reductase inhibitor [29].
• From this we derived estimates of costs of different regimes which are and could be used in TB control in Zambia. Severe reactions occurred in 18.7% of all HIV seropositive patients receiving thiacetazone, fatally so in 1.2% (odds ratio 16.6) [30].

Analytical, diagnostic and therapeutic context of Thioacetazon

• Inhibition of plaque formation by thiacetazone in an MDCK cell culture that had been infected with the influenza A/WSN/33 virus was demonstrated [31].
• Fifty-four strains of M. tuberculosis complex were characterised based on the minimum inhibitory concentration (MIC) of thiacetazone and the growth pattern in the presence of different concentrations of the drug [32].
• Risk for relapse in HIV-infected adults with pulmonary TB after treatment with a nine month rifampicin-containing regimen was low (3.1 per 100 person-years observation) compared with those treated with a thiacetazone-containing regimen (10.1 per 100 person-years observation) [33].
• Twelve zinc(II) complexes with thiosemicarbazone and semicarbazone ligands were prepared and characterized by elemental analysis, thermogravimetric and differential thermal analysis (TG/DTA), FT-IR and 1H and 13C NMR spectroscopy [34].
• DESIGN: Nested case-control study within a randomized prospective clinical trial comparing the safety and efficacy of thiacetazone- and rifampicin-containing regimens for TB treatment in HIV-infected adults [33].

References