A Rapid Method for the Evaluation of New Antituberculous Agents

Ashtekar, Dilip R.; Fernandes, Fábio S.; Khadse, B. G.; Shirodkar, M.V.N.

doi:10.1159/000238472

Cited by 24 publications

(9 citation statements)

References 3 publications

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“…However, although results are generally available in 5 days, the tests performed on the BACTEC system are costly and are not suited to the evaluation of large numbers of compounds. An alternative method for in vitro testing was described by Ashtekar et al (1) We are seeking to identify novel molecules which possess antimycobacterial activity. The slow growth rate and, more importantly, the highly infectious nature of M. tuberculosis preclude its use in a high-throughput screen.…”

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High-throughput screen for detecting antimycobacterial agents

Chung

Aktar

Jackson

et al. 1995

Antimicrob Agents Chemother

103

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A simple, robust assay system which can be used to screen for inhibitors of mycobacterial growth has been developed. A strain of the rapidly growing saprophyte Mycobacterium aurum is used as the test organism. Inhibition of its growth is highly predictive of activity against Mycobacterium tuberculosis, which cannot itself be used in screening because of its growth characteristics and highly infectious nature. The viability of M. aurum in the presence of a test sample is monitored by measuring the uptake of radiolabelled uracil into the cells. In a microtiter plate format, the screen has the potential for testing several thousand samples per day.Tuberculosis has reemerged in recent years as a serious public health problem (3,11,14). The resurgence has been linked to coinfection with the human immunodeficiency virus (2) and to the emergence of strains resistant to available therapies (10). Multidrug-resistant Mycobacterium tuberculosis is refractory to treatment with any of the commonly available drugs, so new classes of compound are needed to counter the threat posed by these strains. In addition, new drugs are required. These drugs will need to have improved pharmacokinetic properties which reduce the frequency and/or duration of therapy and a broader spectrum of antimycobacterial activity to include emerging pathogens such as Mycobacterium avium.The first proportional methods used to determine mycobacterial susceptibility were developed in the 1950s (4, 13). Conventional antibiotic susceptibility testing protocols were developed from these methods and include testing on both solid and liquid media. Solid media have included Lowenstein-Jensen (4) and Middlebrook 7H11 (12) agars. Several problems are inherent in this type of assay, including drug instability (long incubation period and protein binding of drug affect potency), binding of drug to some medium components, and contamination by extraneous microorganisms, and because of the slow growth rate of M. tuberculosis, it may take up to 3 weeks to obtain a result. A microdilution MIC method with Middlebrook 7H9 broth has been developed (22), but it still takes 2 weeks to produce macroscopic growth.BACTEC is a rapid, radiometric, broth susceptibility system which is now routinely used to measure drug susceptibilities (7)(8)(9)(17)(18)(19) We are seeking to identify novel molecules which possess antimycobacterial activity. The slow growth rate and, more importantly, the highly infectious nature of M. tuberculosis preclude its use in a high-throughput screen. Thus, we have developed a rapid and sensitive broth susceptibility system using a strain of the rapidly growing, nonpathogenic organism Mycobacterium aurum. This assay offers the possibility of screening large numbers of compounds in a system which is highly predictive of activity against M. tuberculosis. MATERIALS AND METHODSMedia and supplements. Middlebrook 7H11 agar and Middlebrook 7H9 broth (5) (Difco, West Molesey, United Kingdom) were prepared as described in the Difco Manual (6). The supplements OADC (...

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confidence: 99%

High-throughput screen for detecting antimycobacterial agents

Chung

Aktar

Jackson

et al. 1995

Antimicrob Agents Chemother

103

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“…The success with these compounds stimulated the search for new biologically active derivatives (17) On the other hand, sulfur and/or nitrogen heterocycles that possess pharmaceutical activities widely occur in nature in the form of alkaloids, vitamins, pigments and as constituents of plant and animal cells. (18)(19)(20).…”

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Synthesis of some novel Carbazole derivatives and evaluation of their antimicrobial activity

Kaplancıklı¹

2011

mpj

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Carbazole and its derivatives are an important type of nitrogen containing aromatic heterocyclic compounds which have attracted considerable attention of medicinal chemists due to their antimicrobial activities. For this purpose, new carbazole derivatives were synthesized and evaluated for antimicrobial activity. As starting material 2-chloro-N-(9-ethyl-9H-carbazol-3-yl)acetamide was prepared by the reaction of 3-amino-9-ethyl-9H-carbazole with chloroacetyl chloride. The reaction of 2-chloro-N-(9-ethyl-9H-carbazol-3-yl)acetamide with appropriate mercapto-heterocyclics resulted in the formation of the title compounds. The chemical structures of the compounds were elucidated by IR, 1H-NMR, FAB-MS spectral data and elemental analysis. Their antimicrobial activities against Candida albicans (two strains), Candida glabrata, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa were investigated.

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“…Radiometric : BACTEC 460® instrument is a semi-automated radiometric drug susceptibility testing (RAD) method that measures the 14 CO 2 produced by metabolic breakdown of (1- 14 C) palmitic acid in a liquid Middlebrook 7H12 medium (4, 16, 42). With this method, multiple concentrations can be tested and an MIC calculated (16).…”

Section: Introductionmentioning

confidence: 99%

Antimycobacterial susceptibility testing methods for natural products research

Bueno¹,

Kouznetsov²

2010

Braz. J. Microbiol.

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The emergence of multidrug-resistant strains of Mycobacterium tuberculosis underscores the need of continuous developments on new and efficient methods to determine the susceptibility of isolates of M. tuberculosis in the search for novel antimicrobial agents. Natural products constitute an important source of new drugs, but design and implementation of antimycobacterial susceptibility testing methods are necessary for evaluate the different extracts and compounds. A number of biological assay methodologies are in current use, ranging from the classical disk diffusion and broth dilution assay format, to radiorespirometric (BACTEC), dye-based, and fluorescent/luminescence reporter assays. This review presents an analysis on the in vitro susceptibility testing methods developed for determinate antitubercular activity in natural products and related compounds (semi-synthetic natural products and natural products-derived compounds) and the criteria to select the adequate method for determination of biological activity of new natural products.

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A Rapid Method for the Evaluation of New Antituberculous Agents

Cited by 24 publications

References 3 publications

High-throughput screen for detecting antimycobacterial agents

High-throughput screen for detecting antimycobacterial agents

Synthesis of some novel Carbazole derivatives and evaluation of their antimicrobial activity

Antimycobacterial susceptibility testing methods for natural products research

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