Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis, Characterization and Biological Evaluation of New 3,5-Disubstituted-Pyrazoline Derivatives as Potential Anti-Mycobacterium tuberculosis H37Ra Compounds.

ABSTRACT: A total of fourteen pyrazoline derivatives were synthesized through cyclo-condensation reactions by chalcone derivatives with different types of semicarbazide. These compounds were characterized by IR, 1D-NMR (¹H, ¹³C and Distortionless Enhancement by Polarization Transfer - DEPT-135) and 2D-NMR (COSY, HSQC and HMBC) as well as mass spectroscopy analysis (HRMS). The synthesized compounds were tested for their antituberculosis activity against Mycobacterium tuberculosis H37Ra in vitro. Based on this activity, compound 4a showed the most potent inhibitory activity, with a minimum inhibitory concentration (MIC) value of 17 μM. In addition, six other synthesized compounds, 5a and 5c-5g, exhibited moderate activity, with MIC ranges between 60 μM to 140 μM. Compound 4a showed good bactericidal activity with a minimum bactericidal concentration (MBC) value of 34 μM against Mycobacterium tuberculosis H37Ra. Molecular docking studies for compound 4a on alpha-sterol demethylase was done to understand and explore ligand-receptor interactions, and to hypothesize potential refinements for the compound.

SUBMITTER: Wong KT

PROVIDER: S-EPMC8038544 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Proteome of Mycobacterium tuberculosis treated with 2,4-disubstituted pyridine derivatives

Project description:Two selected compounds, 2,4-disubstituted pyridine derivatives (11 and 15), revealed significant bactericidal activity against Mycobacterium tuberculosis deposited within human macrophages as well as against biofilm-forming tubercle bacilli. The mass spectrometry-based proteomics (LC-MS/MS) of the wild-type tubercle bacilli growing in the subinhibitory concentration of 11 or 15 revealed 15 overproduced proteins not detectable in the control cells including virulence-related proteins.

2022-11-02 | PXD035807 | Pride

Imidazole-Thiosemicarbazide Derivatives as Potent Anti-Mycobacterium tuberculosis Compounds with Antibiofilm Activity.

Project description:Mycobacterium tuberculosis (Mtb) is an intracellular pathogenic bacterium and the causative agent of tuberculosis. This disease is one of the most ancient and deadliest bacterial infections, as it poses major health, social and economic challenges at a global level, primarily in low- and middle-income countries. The lack of an effective vaccine, the long and expensive drug therapy, and the rapid spread of drug-resistant strains of Mtb have led to the re-emergence of tuberculosis as a global pandemic. Here, we assessed the in vitro activity of new imidazole-thiosemicarbazide derivatives (ITDs) against Mtb infection and their effects on mycobacterial biofilm formation. Cytotoxicity studies of the new compounds in cell lines and human monocyte-derived macrophages (MDMs) were performed. The anti-Mtb activity of ITDs was evaluated by determining minimal inhibitory concentrations of resazurin, time-kill curves, bacterial intracellular growth and the effect on biofilm formation. Mutation frequency and whole-genome sequencing of mutants that were resistant to ITDs were performed. The antimycobacterial potential of ITDs with the ability to penetrate Mtb-infected human macrophages and significantly inhibit the intracellular growth of tubercle bacilli and suppress Mtb biofilm formation was observed.

| S-EPMC8700351 | biostudies-literature

Mycobacterium tuberculosis microarray to screen anti-tuberculosis compounds

Project description:Feature reduction of microarray data from mycobacteria treated with a variety of various clinical and investigational drugs

2013-04-24 | GSE46212 | GEO

Mycobacterium tuberculosis microarray to screen anti-tuberculosis compounds

Project description:Feature reduction of microarray data from mycobacteria treated with a variety of various clinical and investigational drugs We are using feature reduction to demonstrate that subsets of biomarker genes representative of the whole genome are sufficient for MOA classification and deconvolution in a medium-throughput microfluidic format ultimately leading to a cost effective and rapid tool for routine antibacterial drug-discovery programs.

2013-04-24 | E-GEOD-46212 | biostudies-arrayexpress

PBMCs exposed to the Mycobacterium tuberculosis H37Ra strain

Project description:Human peripheral blood mononuclear cells were cultured in presence of H37Ra strain at 37oC, 5%CO2. Cellular aggregates were collected at 24h, and RNA extracted and hybridized to Affymetrix microarrays (HG-U133). Raw data from microarray experiments was analyzed with dCHIP and SAM programs to determine the significance of changes at the biological context. PBMCs were exposed in triplicate to H37Ra strain. PBMCs from the same donor were cultured in triplicate at the same conditions than treated samples. RNA was extracted from each sample and hybridized to Affymetrix Human arrays.

2014-05-28 | E-GEOD-16250 | biostudies-arrayexpress

Comparison of membrane proteins of Mycobacterium tuberculosis H37Rv and H37Ra strains.

Project description:BackgroundThe potential causes for variation in virulence between distinct M. tuberculosis strains are still not fully known. However, differences in protein expression are probably an important factor. In this study we used a label-free quantitative proteomic approach to estimate differences in protein abundance between two closely related M. tuberculosis strains; the virulent H37Rv strain and its attenuated counterpart H37Ra.ResultsWe were able to identify more than 1700 proteins from both strains. As expected, the majority of the identified proteins had similar relative abundance in the two strains. However, 29 membrane-associated proteins were observed with a 5 or more fold difference in their relative abundance in one strain compared to the other. Of note, 19 membrane- and lipo-proteins had higher abundance in H37Rv, while another 10 proteins had a higher abundance in H37Ra. Interestingly, the possible protein-export membrane protein SecF (Rv2586c), and three ABC-transporter proteins (Rv0933, Rv1273c and Rv1819c) were among the more abundant proteins in M. tuberculosis H37Rv.ConclusionOur data suggests that the bacterial secretion system and the transmembrane transport system may be important determinants of the ability of distinct M. tuberculosis strains to cause disease.

| S-EPMC3033788 | biostudies-literature

Mycobacterium tuberculosis H37Ra

Project description:An attenuated strain used in mycobacterial virulence research

| PRJNA18649 | ENA

Mycobacterium tuberculosis H37Ra

Project description:Reprogramming the endogenous type III-A CRISPR-Cas system for genome editing and RNA interference in Mycobacterium tuberculosis

| PRJNA401651 | ENA

Mycobacterium tuberculosis H37Ra

Project description:Mycobacterium tuberculosis Raw sequence reads

| PRJNA391218 | ENA

Mycobacterium tuberculosis H37Ra

Project description:Mycobacterium tuberculosis H37Ra genome sequencing and assembly

| PRJNA329548 | ENA