New Isoniazid Complexes, Promising Agents Against Mycobacterium tuberculosis

Tuberculosis (TB) is a public health disease that produces several million deaths annually worldwide. Due to this critical situation and the appearance of drug-resistant microbial strains, innovation in TB drug discovery is a research priority. In this work, the synthesis and characterization by elemental analysis, hermogravimetry, conductimetric measurements and spectroscopies UV-Vis, IR and EPR of [Cu(INH)(H2O)]SO4⋅2H2O (Cu-INH) and [CoCl(INH)2(H2O)] Cl⋅2.5H2O (Co-INH) complexes with isoniazid (INH) are reported. Besides, the lipophilicity, the activity against Mycobacterium tuberculosis (MICCu-INH = 0.78 μg/mL and MICCo-INH = 0.19 μg/mL) and the cytotoxicity (IC50 = 48.8 and 625 μg/mL for the copper and cobalt complexes, respectively) were measured and the selectivity index (62.5 for Cu-INH and 3205 for Co-INH) was calculated. These results indicate that these complexes are good candidates for further studies.

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Genetic diversity and drug susceptibility patterns of the Mycobacterium tuberculosis complex in Yunnan, China

Bioscience Reports ◽

10.1042/bsr20181746 ◽

2019 ◽

Vol 39 (5) ◽

Author(s):

Ruolan Bai ◽

Shuijing Chi ◽

Xiaofei Li ◽

Xiting Dai ◽

Zhenhua Ji ◽

...

Keyword(s):

Public Health ◽

Genetic Diversity ◽

Mycobacterium Tuberculosis ◽

Public Health Problem ◽

Drug Susceptibility ◽

Drug Resistant ◽

Global Public Health ◽

High Genetic Diversity ◽

Dominant Feature ◽

Mdr Tb

AbstractTuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) which has been threatening global public health for many years. High genetic diversity is dominant feature of Mtb. Increasing cases of multidrug-resistant (MDR) tuberculosis (MDR-TB) is a serious public health problem to TB control in China. Spontaneous mutations in the Mtb genome can alter proteins which are the target of drugs, making the bacteria drug resistant. The purpose of the present study was to analyze the genotype of Mtb isolates from some areas in Yunnan, China and explore the association between genotypes and MDR-TB. Using spoligotyping, we identified Beijing genotypes, six non-Beijing genotypes and a number of orphan genotypes from 270 Mtb isolates from patients in Yunnan Province during 2014–2016. Of 270 Mtb isolates, 102 clinical Mtb strains were identified as drug-resistant (DR) by drug susceptibility testing (DST), among them, 52 MDR strains. Beijing genotypes occupied the highest MDR proportion (78.85%) followed by the orphan genotypes (15.38%). The characteristics of MDR strains showed high genetic diversity. The results will help to efficiently improve diagnosis and treatment and provide valuable information for Mtb molecular epidemiology.

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Isoniazid, The Frontline of Resistance in Mycobacterium tuberculosis

McGill Journal of Medicine ◽

10.26443/mjm.v6i2.686 ◽

2002 ◽

Vol 6 (2) ◽

Author(s):

James B. Whitney ◽

Mark A. Wainberg

Keyword(s):

Public Health ◽

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Genome Sequence ◽

Molecular Mechanisms ◽

Close Association ◽

Drug Resistant ◽

Efficient Control ◽

Control And Management ◽

Developed Nations

Tuberculosis is an ancient disease that has held close association with humans for millennia. Through persistence, this remarkably successful organism has managed to infect an estimated third of the world's population. Declining rates of tuberculosis in developed nations have masked an emerging epidemic of drug resistant cases that have been reported in almost every country under scrutiny. The recent completion of the genome sequence of Mycobacterium tuberculosis has mandated more efficient control and management of this disease. The momentum for this public health imperative will come from information gleaned from advances in genomics and related technologies towards deciphering molecular mechanisms of mycobacterial drug resistance.

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Hybridization approach to drug discovery inhibiting Mycobacterium tuberculosis. An overview.

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200819151342 ◽

2020 ◽

Vol 20 ◽

Author(s):

Daniele Zampieri ◽

Maria G. Mamolo

Keyword(s):

Mycobacterium Tuberculosis ◽

Drug Discovery ◽

Cause Of Death ◽

Medicinal Chemistry ◽

Causes Of Death ◽

Infectious Agent ◽

Drug Resistant ◽

New Chemical Entities ◽

Hybrid Ligands

: Tuberculosis is one of the top 10 causes of death worldwide and the leading cause of death from a single infectious agent mainly due to Mycobacterium tuberculosis (MTB). Recently, clinical prognoses have worsened due to the emergence of multi-drug resistant (MDR) and extensive-drug resistant (XDR) tuberculosis which lead to the need of new, efficient and safely drugs. Among the several strategies, polypharmacology could be considered one of the best solutions, in particular the multi-target directed ligands strategy (MTDLs), based on the synthesis of hybrid ligands acting against two targets of the pathogen. The framework strategy comprises linking, fusing and merging approaches to develop new chemical entities. With these premises, this review aims to provide an overview of recent hybridization approach, in medicinal chemistry, of the most recent and promising multitargeting antimycobacterial candidates.

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Tailored-pharmacophore model to enhance virtual screening and drug discovery: a case study on the identification of potential inhibitors against drug-resistant Mycobacterium tuberculosis (3R)-hydroxyacyl-ACP dehydratases

Future Medicinal Chemistry ◽

10.4155/fmc-2017-0020 ◽

2017 ◽

Vol 9 (10) ◽

pp. 1055-1071 ◽

Cited By ~ 5

Author(s):

Kgothatso E Machaba ◽

Ndumiso N Mhlongo ◽

Yussif M Dokurugu ◽

Mahmoud ES Soliman

Keyword(s):

Mycobacterium Tuberculosis ◽

Drug Discovery ◽

Virtual Screening ◽

Pharmacophore Model ◽

Drug Resistant ◽

Potential Inhibitors

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Study of the Effectiveness against Test Strain Mycobacterium terrae DSM 43227 of Some Substances Containing Fragment of Phenolic

Epidemiology and Vaccinal Prevention ◽

10.31631/2073-3046-2016-15-4-37-41 ◽

2016 ◽

Vol 15 (4) ◽

pp. 37-41

Author(s):

T. A. Grenkova ◽

A. I. Chizhov ◽

M. P. Gusarova ◽

N. V. Gudova

Keyword(s):

Public Health ◽

Mycobacterium Tuberculosis ◽

Phenolic Compounds ◽

Medical Devices ◽

Test Strain ◽

Drug Resistant ◽

Phenol Compounds ◽

Low Concentrations ◽

The World ◽

Active Substances

Relevance. Multi-drug-resistant Mycobacterium tuberculosis has been an important problem in public health around the world. However, development of effective methods and means of disinfection is now extremely urgent. Phenol is probably the oldest known disinfectant. Disinfectants based on substances containing phenolic practically used in almost every countries of the worldwide for the disinfection of medical devices, surfaces and hand hygiene. Goal. Comparative study of the activity of certain disinfectants containing phenol fragment against the test strain. Materials and methods. Multi-drug-resistant M. terrae, M. avium-intracellulara and M. tuberculosis have similar characteristics of resistance to chemical disinfectants, herefore M. terrae DSM 43227 used as the test strain. We studied five used in Russia for the production of disinfectants and antiseptics. substances containing a phenolic. Results. The disinfectant effect of substances with phenol compounds was detected in lower concentrations (from 0.02% for 2-benzil-4-chlorphenol to 1.0% for ortophenylphenol) than with substances containing glutaraldehyde or chloramine B compounds. Conclusions. Saving disinfecting effectiveness at low concentrations of the active substances in the working solutions can be recommended disinfectants based on phenolic compounds for disinfection measures in the complex of measures for prevention of occurrence and spread of tuberculosis.

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