The Chemotherapy of Experimental Tuberculosis I

Donovick, Richard; Pansy, Felix; Stryker, Gladys; Bernstein, Jack

doi:10.1128/jb.59.5.667-674.1950

Cited by 51 publications

(8 citation statements)

References 2 publications

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“…Thiosemicarbazide itself failed to show activity in our experiments (cf. also Donovick et al, 1950). The enhanced activity of the p-amino-benzal-thiosemicarbazone derivatives against isoniazid-resistant strains is consistent with the reported findings (Domagk, 1952 ;Barry et al, 1954 a) that such strains are more sensitive to amithiozone (p-acetylamino-benzal-thiosemicarbazone).…”

Section: Experlmental Methodssupporting

confidence: 89%

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SOME NOVEL ANTITUBERCULOSIS AGENTS DERIVED FROM OXIDISED STARCH AND OTHER POLYSACCHARIDES¹

Barry

Conalty

Gaffney

1955

British Journal of Urology

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fhr Lrrhoratorrer (if the Medical Resuurch Colmtrl of lrekrd9 DIdJlltl I NTRODUCTlON POLYSACCHARIDE molecules containing a-glycol groupings are oxidised by the periodate ion, each a-glycol grouping yielding two potential aldehyde groups without extensive degradation of the polysaccharide. The oxidised materials may now be readily condensed with hydrazines, thiosemicarbazones, and other basic reagents. I n this way oxidised potato starch, inulin, and alginic acid have been converted into characteristic polymers by condensation with isoniazid or p-amino-benzaldehyde thiosemicarbazone. These products, Hinstarch and Constarch, from oxystarch and isoniazid or the above thiosemicarbazone, have already been described (Barry et al., 1954 h). The corresponding polymers from oxyinulin and oxyalginic acid have been named Hinulin, Conulin, and Conalg respectively. The structure of Hinstarch, Hinulin, and Hinalg, and some degradative experiments on these products, have been discussed previously (Barry and Mitchell, 1953 a and h). Hinconstarch is a mixed polymer got by condensation of oxystarch with equimolar proportions of isoniazid and p-amino-benzal-thiosemicarbazone (Barry et a]., 1954 h). Thiostarch is obtained by the condensation of oxystarch with thiosemicarbazide.The purpose of the present investigation was to determine the activity of these substances in experimental tuberculosis produced by infection with strains of M~r o . tuberculosis both sensitive and resistant to isoniazid and to determine from considerations of effectiveness and toxicity whether any of them were likely to prove of value as additions to the chemotherapeutic agents in current use in the treatment of tuberculosis. EXPERlMENTAL METHODSScreening in Mice.-Mic~.-Twenty-two to twenty-eight G. Schofield albino mice in groups of ten were used in most of the experiments, but in a few the brown tlhcr strain or the Parkes albino strain was used.Ir@ction.-Nine-day-old cultures of the bovine Ravenel (Rv) strain of M . tuhercii/o.yj.y grown in a modified Proskauer and Beck medium (Conalty, 1954) containing "Tween 80'' (0.05 per cent.) and bovine albumin fraction V (0.1 per cent.) were used to infect the mice intravenously. Infecting dose was 0.1 mg. moist weight (turbidimetric standardisation).In screening for activity against isoniazid resistant strains of M . tuberculosis, three-weeks-old cultures of an isoniazid-resistant variant of Ravenel (Rv), grown on Lowenstein-Jensen medium containing 100 pg. per ml. isoniazid, were lightly ground in Grifith's tubes and suspended in the Proskauer and Beck-tween-albumin medium and standardised.Administration oj' Drugs.-The drugs were administered in a ground biscuit diet for fourteen days, beginning on the day of infection. The food intake, and consequently the drug intake, was measured daily. The daily intake of drug used in the tables is the mean of the daily intakes during the five days, second to the sixth inclusive.

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Section: Experlmental Methodssupporting

confidence: 89%

“…Mitchison (1954) also reported low virulence with highly resistant strains in guinea-pigs. Karlson and Ikemi (1954) have reported findings, rather similar to those described in this paper, with a resistant variant of H37 Rv (resistant to more than 40 pg. per ml.…”

Section: 5supporting

confidence: 89%

SOME NOVEL ANTITUBERCULOSIS AGENTS DERIVED FROM OXIDISED STARCH AND OTHER POLYSACCHARIDES¹

Barry

Conalty

Gaffney

1955

British Journal of Urology

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“…After testing of Conteben in US hospitals, they concluded that "a prompt and thorough series of experimental and clinical trials in the United States" was justified along with experimenting with other thiosemicarbazones [37]. Two US pharmaceutical companies, Hoffman-La Roche and E. R. Squibb & Sons, quickly developed a series of thiosemicarbazone analogs but none showed better activity than Conteben [38][39][40] until the benzene ring in Conteben was replaced with a pyridine ring leading to the simultaneous discovery of Rimifon at Hoffman-La Roche [39] and Nydrazid at Squibb [41]. In parallel, Domagk at Bayer developed the thiosemicarbazone analog Neoteben [42].…”

Section: The Mycobacterial Cell Wallmentioning

confidence: 99%

Mycobacterial Cell Wall: A Source of Successful Targets for Old and New Drugs

Vilchèze

2020

Applied Sciences

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Eighty years after the introduction of the first antituberculosis (TB) drug, the treatment of drug-susceptible TB remains very cumbersome, requiring the use of four drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) for two months followed by four months on isoniazid and rifampicin. Two of the drugs used in this “short”-course, six-month chemotherapy, isoniazid and ethambutol, target the mycobacterial cell wall. Disruption of the cell wall structure can enhance the entry of other TB drugs, resulting in a more potent chemotherapy. More importantly, inhibition of cell wall components can lead to mycobacterial cell death. The complexity of the mycobacterial cell wall offers numerous opportunities to develop drugs to eradicate Mycobacterium tuberculosis, the causative agent of TB. In the past 20 years, researchers from industrial and academic laboratories have tested new molecules to find the best candidates that will change the face of TB treatment: drugs that will shorten TB treatment and be efficacious against active and latent, as well as drug-resistant TB. Two of these new TB drugs block components of the mycobacterial cell wall and have reached phase 3 clinical trial. This article reviews TB drugs targeting the mycobacterial cell wall in use clinically and those in clinical development.

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“…A similar reaction with 2,3-dihydroxybenzaldehyde furnishes the corresponding Schiff base, 2,3dihydroxybenzaldehyde thiosemicarbazone, which possesses two hydroxy substituents ion the aromatic ring. 2,3-Dihydroxybenzaldehyde thiosemicarbazone was reported many years ago (Bernstein et al, 1951;Donovick et al, 1950), and it exhibits useful activity as a chemotherapeutic agent. The compound crystallizes as the title hemihydrate, (I) ( Fig.…”

Section: Commentmentioning

confidence: 99%

2,3-Dihydroxybenzaldehyde thiosemicarbazone hemihydrate

et al. 2006

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The Chemotherapy of Experimental Tuberculosis I

Cited by 51 publications

References 2 publications

SOME NOVEL ANTITUBERCULOSIS AGENTS DERIVED FROM OXIDISED STARCH AND OTHER POLYSACCHARIDES¹

SOME NOVEL ANTITUBERCULOSIS AGENTS DERIVED FROM OXIDISED STARCH AND OTHER POLYSACCHARIDES¹

Mycobacterial Cell Wall: A Source of Successful Targets for Old and New Drugs

2,3-Dihydroxybenzaldehyde thiosemicarbazone hemihydrate

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The Chemotherapy of Experimental Tuberculosis I

Cited by 51 publications

References 2 publications

SOME NOVEL ANTITUBERCULOSIS AGENTS DERIVED FROM OXIDISED STARCH AND OTHER POLYSACCHARIDES1

SOME NOVEL ANTITUBERCULOSIS AGENTS DERIVED FROM OXIDISED STARCH AND OTHER POLYSACCHARIDES1

Mycobacterial Cell Wall: A Source of Successful Targets for Old and New Drugs

2,3-Dihydroxybenzaldehyde thiosemicarbazone hemihydrate

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Product

Resources

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SOME NOVEL ANTITUBERCULOSIS AGENTS DERIVED FROM OXIDISED STARCH AND OTHER POLYSACCHARIDES¹

SOME NOVEL ANTITUBERCULOSIS AGENTS DERIVED FROM OXIDISED STARCH AND OTHER POLYSACCHARIDES¹