scholarly journals The Structural Modeling of the Interaction between Levofloxacin and theMycobacterium tuberculosisGyrase Catalytic Site Sheds Light on the Mechanisms of Fluoroquinolones Resistant Tuberculosis in Colombian Clinical Isolates

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
N. Alvarez ◽  
E. Zapata ◽  
G. I. Mejía ◽  
T. Realpe ◽  
P. Araque ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Multidrug Resistant ◽  
Catalytic Site ◽  
Clinical Isolates ◽  
Isopropyl Group ◽  
Acid Base ◽  
Base Interaction ◽  
Resistant Tuberculosis ◽  
Acetyl Group ◽  
Acid Base Interaction

We compared the prevalence of levofloxacin (LVX) resistance with that of ofloxacin (OFX) and moxifloxacin (MFX) among multidrug resistant (MDR)MTBclinical isolates collected in Medellin, Colombia, between 2004 and 2009 and aimed at unraveling the underlying molecular mechanisms that explain the correlation between QRDR-A mutations and LVX resistance phenotype. We tested 104 MDR isolates for their susceptibility to OFX, MFX, and LVX. Resistance to OFX was encountered in 10 (9.6%) of the isolates among which 8 (7.7%) were also resistant to LVX and 6 (5.7%) to MFX. Four isolates resistant to the 3 FQ were harboring the Asp94Gly substitution, whilst 2 other isolates resistant to OFX and LVX presented the Ala90Val mutation. No mutations were found in the QRDR-B region. The molecular modeling of the interaction between LVX and the DNA-DNA gyrase complex indicates that the loss of an acetyl group in the Asp94Gly mutation removes the acid base interaction with LVX necessary for the quinolone activity. The Ala90Val mutation that substitutes a methyl for an isopropyl group induces a steric modification that blocks the LVX access to the gyrase catalytic site.

Assessing the utility of three TaqMan probes for the diagnosis of tuberculosis and resistance to rifampin and isoniazid in Veracruz, México

2012 ◽  
Vol 58 (3) ◽  
pp. 318-325 ◽  
Author(s):  
Roberto Zenteno-Cuevas ◽  
Betzaida Cuevas-Cordoba ◽  
Antonio Enciso ◽  
Leonor Enciso ◽  
Aremy Cuellar
Keyword(s):  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Rpob Gene ◽  
Diagnostic Value ◽  
Multidrug Resistant ◽  
Molecular Probes ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Taqman Probes ◽  
Resistant Tuberculosis

Mutations at codons 526 and 531 in the rpoB gene and at 315 in the katG gene are considered diagnostic markers for resistance to rifampin and isoniazid in tuberculosis. The aim of this study was to design and evaluate three TaqMan probes for the identification of these mutations in 138 respiratory samples positive for acid-fast bacilli, and 32 clinical isolates from a region with considerable levels of drug resistance. The specificities of the probes for the diagnosis of resistance to both drugs were 100%; however, the sensitivities were calculated to be 50% for isoniazid and 56% for rifampin. DNA sequencing of rpoB and katG; and the spoligotyping assay of the clinical isolates, confirmed the diversity of the mutations and the presence of 11 spoligotypes with a shared international type and eight unique spoligotypes. Analysis of the respiratory samples identified 22 (16%) as drug-resistant and 4 (3%) as multidrug-resistant tuberculosis. The diagnostic value of the TaqMan probes was compromised by the diversity of mutations found in the clinical isolates. This highlights the need for better understanding of the molecular mechanisms responsible for drug resistance prior to the use of molecular probes, especially in regions with significant levels of drug-resistant tuberculosis.

scholarly journals SPECIFIC NATURE OF ACID-BASE INTERACTION OF OCTA(4-TERT-BUTYLPHENYL)TETRAPYRAZINOPORPHYRAZINE WITH ORGANIC PROTON-ACCEPTOR MOLECULES IN BENZENE

2021 ◽  
Vol 64 (3) ◽  
pp. 33-40
Author(s):  
Oleg A. Petrov ◽  
Aleksandr S. Semeykin ◽  
Mariya V. Shilovskaya ◽  
Tatiana V. Lyubimova
Keyword(s):  
Proton Transfer ◽  
Proton Acceptor ◽  
Base System ◽  
Excess Charge ◽  
Hydrogen Atoms ◽  
Acid Base ◽  
Base Interaction ◽  
Base Equilibrium ◽  
Acid Base Equilibrium ◽  
Acid Base Interaction

The reaction of acid-base interaction of octa(4-tert-butylphenyl)tetrapyrazinophosphyrazine with pyridine, 2-methylpyridine, morhpoline, pipyridine, n-butylamine, tert-butylamine, diethylamine, triethylamine and dimethylsulfoxide in benzene was investigated. It is shown that the researched porphyrazine forms kinetically stable proton transfer complexes with pyridine, 2-methylpyridine, morpholine and dimethylsulfoxide. In benzene-base system an acid-base equilibrium between the molecular form of octa(4-tert-butylphenyl)tetrapyrazinoporphyrazine and its proton transfer complex was established. The interaction of substituted tetrapyrazinoporphyrazine with morpholine in benzene was revealed to be a kinetically controllable process which occurs with low reaction rate and high values of activation energy. Such values are not inherent to most of relatively simple liquid-phase acid-base systems. The kinetic equation of the process was found, and, based on the spectral changes accompanying the reaction, a cheme of two-stage process of proton transfer of NH-groups of octa(4-tert-butylphenyl)tetrapyrazinoporphyrazine to morpholine in benzene was proposed. A possible structure of proton transfer complex of octa(4-tert-butylphenyl)tetrapyrazinoporphyrazine with organic bases is shown. In these complexes the inner hydrogen atoms of the cycle, bonded with base molecules, lie under and above the plane of the molecule, and the proton transfer from acid to base is limited either by the H-complex or the ion-ion associates constituting an H-bonded ion pair. Depending on the proton accepting tendency of the base, the acid-base equilibrium can shift towards or away from the more or less polarized structure. It was revealed that in benzene - n-butylamine (tri-butylamine, diethylamine, triethylamine, pipyridine) system the acid-base interaction involving octa(4- tert-butylphenyl)tetrapyrazinoporphyrazine occurs incredibly fast, with rates not measurable by standard spectrophotography methods. The forming proton transfer complexes are highly labile due to concurrent proton reaction occurring, leading to the formation of dianion form of octa(4- tert-butylphenyl)tetrapyrazinoporphyrazine. This form undergoes spontaneous dissolution into low-molecular colorless products due to the lack of compensation of excess charge in the macrocycle.

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