Hydrazone, benzohydrazones and isoniazid-acylhydrazones as potential antituberculosis agents

2019 ◽  
Vol 14 (11) ◽  
pp. 981-994 ◽  
Author(s):  
Eloísa G Sampiron ◽  
Giovana F Costacurta ◽  
Vanessa P Baldin ◽  
Aryadne L Almeida ◽  
Andressa L Ieque ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Ethidium Bromide ◽  
High Selectivity ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Selectivity Index ◽  
Clinical Isolates ◽  
Antituberculosis Activity ◽  
Bactericidal Activities ◽  
Limited Spectrum

Aim: To evaluate the potential of three benzohydrazones (1–3), four acylhydrazones derived from isoniazid (INH-acylhydrazones) (4–7) and one hydrazone (8) as antituberculosis agents. Materials & methods: Inhibitory and bactericidal activities were determined for the reference Mycobacterium tuberculosis ( Mtb) strain and clinical isolates. Cytotoxicity, drug combinations and ethidium bromide accumulation assays were also performed. Results: The tested compounds (1–8) presented excellent antituberculosis activity with surprisingly inhibitory (0.12–250 μg/ml) and bactericidal values, even against multidrug-resistant Mtb clinical isolates. Compounds showed high selectivity index, with values reaching 1833.33, and a limited spectrum of activity. Some of the compounds (2 & 8) are also great inhibitors of bacillus efflux pumps. Conclusion: Benzohydrazones and INH-acylhydrazones may be considered scaffolds for the development of new anti- Mtb drugs.

Rescue of streptomycin activity by piperine in Mycobacterium tuberculosis

2021 ◽  
Author(s):  
Leonora L Calsavara ◽  
Laíse A Hegeto ◽  
Eloisa G Sampiron ◽  
Giovana F Costacurta ◽  
Letícia S Murase ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Minimum Inhibitory Concentration ◽  
Ethidium Bromide ◽  
Inhibitory Concentration ◽  
Efflux Pumps ◽  
Clinical Isolates ◽  
Relative Quantification

Aim: To evaluate the modulatory effect of piperine (PIP) on streptomycin (SM) activity in Mycobacterium tuberculosis ( Mtb). Materials & methods: SM and PIP minimum inhibitory concentration (MIC) and combinatory activity were determined in Mtb H37Rv and in susceptible and resistant clinical isolates. Ethidium bromide accumulation assay and relative quantification of efflux pumps genes ( rv1258c, rv1218c and rv2942), after SM and SM+PIP combination exposure, were also performed. Results: PIP concentration of 25 μg/ml (1/4× MIC) was able to inhibit efflux pumps activity, to modulate SM activity in Mtb, and conducted changes in the relative quantification of efflux pumps genes. Conclusion: SM+PIP combination was able to rescue the SM susceptible MIC values in SM resistant Mtb.

scholarly journals In Vitro Activities of Cloxyquin (5-Chloroquinolin-8-ol) against Mycobacterium tuberculosis

2006 ◽  
Vol 51 (3) ◽  
pp. 1105-1106 ◽  
Author(s):  
Poonpilas Hongmanee ◽  
Kamolchanok Rukseree ◽  
Benjamas Buabut ◽  
Boontiwa Somsri ◽  
Prasit Palittapongarnpim
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Antituberculosis Activity

ABSTRACT The in vitro activities of cloxyquin (5-chloroquinolin-8-ol) against 9 standard strains and 150 clinical isolates of Mycobacterium tuberculosis were studied. The MICs ranged from 0.062 to 0.25 μg/ml. The MIC50 and MIC90 were 0.125 and 0.25 μg/ml, respectively. These indicate that cloxyquin exhibited good antituberculosis activity, even for multidrug-resistant isolates.

scholarly journals Detection of mutations associated with isoniazid resistance in multidrug-resistant Mycobacterium tuberculosis clinical isolates

2014 ◽  
Vol 69 (9) ◽  
pp. 2369-2375 ◽  
Author(s):  
Tomasz Jagielski ◽  
Zofia Bakuła ◽  
Katarzyna Roeske ◽  
Michał Kamiński ◽  
Agnieszka Napiórkowska ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Isoniazid Resistance ◽  
Detection Of Mutations

scholarly journals Molecular Investigation of Resistance to the Antituberculous Drug Ethionamide in Multidrug-Resistant Clinical Isolates ofMycobacterium tuberculosis

2010 ◽  
Vol 55 (1) ◽  
pp. 355-360 ◽  
Author(s):  
F. Brossier ◽  
N. Veziris ◽  
C. Truffot-Pernot ◽  
V. Jarlier ◽  
W. Sougakoff
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Drug Targets ◽  
Nadh Dehydrogenase ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Cell Wall Biosynthesis ◽  
Molecular Investigation ◽  
Antituberculous Drug ◽  
Resistant Cells

ABSTRACTEthionamide (ETH) needs to be activated by the mono-oxygenase EthA, which is regulated by EthR, in order to be active againstMycobacterium tuberculosis. The activated drug targets the enzyme InhA, which is involved in cell wall biosynthesis. Resistance to ETH has been reported to result from various mechanisms, including mutations altering EthA/EthR, InhA and its promoter, the NADH dehydrogenase encoded byndh, and the MshA enzyme, involved in mycothiol biosynthesis. We searched for such mutations in 87 clinical isolates: 47 ETH-resistant (ETHr) isolates, 24 ETH-susceptible (ETHs) isolates, and 16 isolates susceptible to ETH but displaying an intermediate proportion of resistant cells (ETHSip; defined as ≥1% but <10% resistant cells). In 81% (38/47) of the ETHrisolates, we found mutations inethA,ethR, orinhAor its promoter, which mostly corresponded to new alterations inethAandethR. The 9 ETHrisolates without a mutation in these three genes (9/47, 19%) had no mutation inndh, and a single isolate had a mutation inmshA. Of the 16 ETHSipisolates, 7 had a mutation inethA, 8 had no detectable mutation, and 1 had a mutation inmshA. Finally, of the 24 ETHsisolates, 23 had no mutation in the studied genes and 1 displayed a yet unknown mutation in theinhApromoter. Globally, the mechanism of resistance to ETH remained unknown for 19% of the ETHrisolates, highlighting the complexity of the mechanisms of ETH resistance inM. tuberculosis.

scholarly journals Ethidium Bromide MIC Screening for Enhanced Efflux Pump Gene Expression or Efflux Activity in Staphylococcus aureus

2010 ◽  
Vol 54 (12) ◽  
pp. 5070-5073 ◽  
Author(s):  
Diixa Patel ◽  
Christos Kosmidis ◽  
Susan M. Seo ◽  
Glenn W. Kaatz
Keyword(s):  
Staphylococcus Aureus ◽  
Ethidium Bromide ◽  
Efflux Pump ◽  
Large Strain ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Reverse Transcription Pcr ◽  
Biocide Resistance ◽  
Straightforward Method ◽  
Short Period

ABSTRACT Multidrug resistance efflux pumps contribute to antimicrobial and biocide resistance in Staphylococcus aureus. The detection of strains capable of efflux is time-consuming and labor-intensive using currently available techniques. A simple and inexpensive method to identify such strains is needed. Ethidium bromide is a substrate for all but one of the characterized S. aureus multidrug-resistant (MDR) efflux pumps (NorC), leading us to examine the utility of simple broth microtiter MIC determinations using this compound in identifying efflux-proficient strains. Quantitative reverse transcription-PCR identified the increased expression of one or more MDR efflux pump genes in 151/309 clinical strains (49%). Ethidium bromide MIC testing was insensitive (48%) but specific (92%) in identifying strains with gene overexpression, but it was highly sensitive (95%) and specific (99%) in identifying strains capable of ethidium efflux. The increased expression of norA with or without other genes was most commonly associated with efflux, and in the majority of cases that efflux was inhibited by reserpine. Ethidium bromide MIC testing is a simple and straightforward method to identify effluxing strains and can provide accurate predictions of efflux prevalence in large strain sets in a short period of time.

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