Dataset Information

Toward antituberculosis drugs: in silico screening of synthetic compounds against Mycobacterium tuberculosisl,d-transpeptidase 2.

ABSTRACT: Mycobacterium tuberculosis (Mtb) the main causative agent of tuberculosis, is the main reason why this disease continues to be a global public health threat. It is therefore imperative to find a novel antitubercular drug target that is unique to the structural machinery or is essential to the growth and survival of the bacterium. One such target is the enzyme l,d-transpeptidase 2, also known as LdtMt2, a protein primarily responsible for the catalysis of 3?3 cross-linkages that make up the mycolyl-arabinogalactan-peptidoglycan complex of Mtb. In this study, structure-based pharmacophore screening, molecular docking, and in silico toxicity evaluations were employed in screening compounds from a database of synthetic compounds. Out of the 4.5 million database compounds, 18 structures were identified as high-scoring, high-binding hits with very satisfactory absorption, distribution, metabolism, excretion, and toxicity properties. Two out of the 18 compounds were further subjected to in vitro bioactivity assays, with one exhibiting a good inhibitory activity against the Mtb H37Ra strain.

SUBMITTER: Billones JB

PROVIDER: S-EPMC4795573 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Toward antituberculosis drugs: in silico screening of synthetic compounds against Mycobacterium tuberculosisl,d-transpeptidase 2.

Billones Junie B JB Carrillo Maria Constancia O MC Organo Voltaire G VG Macalino Stephani Joy Y SJ Sy Jamie Bernadette A JB Emnacen Inno A IA Clavio Nina Abigail B NA Concepcion Gisela P GP

Drug design, development and therapy 20160311

Mycobacterium tuberculosis (Mtb) the main causative agent of tuberculosis, is the main reason why this disease continues to be a global public health threat. It is therefore imperative to find a novel antitubercular drug target that is unique to the structural machinery or is essential to the growth and survival of the bacterium. One such target is the enzyme l,d-transpeptidase 2, also known as LdtMt2, a protein primarily responsible for the catalysis of 3→3 cross-linkages that make up the mycol ...[more]

PMID: 27042006

Similar Datasets

Project description:BackgroundThe prolonged use of antibiotic viz., tetracycline, quinolones, ampicillin, etc., to reduce the infection of cholera, may failed due to the emergence of new Vibrio cholerae antibiotics resistant strains. Moreover, these antibiotics even restricted for patient suffering from severe dehydration. Hence, there is a call to find an alternative therapeutics against V. cholerae. The natures serve different herbs in its lap which might contain several natural therapeutic compounds almost all diseases. Computer-aided designing is the initial steps for screening the novel inhibitors.ObjectiveTo identify and evaluate natural compounds with low side effects with high efficacy against V. cholerae has been done.Materials and methodsIn silico screening, absorption, digestion, metabolism, and excretion (ADME), and docking of herbal compounds have been performed on to the target ToxT (transcriptional activator of V. cholerae). The compound with good ADME properties and drug-likeness property were subjected to docking.ResultsFrom 70 herbal compounds, some compounds such as aloin, campesterol, lupeol, and ursolic acid showed a violation of the rule of five and compounds such as lupeol and beta carotene showed negative binding energy. Luteolin, catechin, brevifolin, etc., compounds were selected based on ADME, drug-likeness property, and docking studies.ConclusionTwo compounds named catechin and luteolin showed better inhibition properties against ToxT and good ADME and drug-likeness property were selected as a better lead molecule for drug development in future. The Genetic Optimization for Ligand Docking fitness score for catechin is 48.74 kcal/mol and luteolin 38.12 kcal/mol.SummaryVibrio cholerae became antibiotic resistance and associated with several cholera epidemic and pandemic. Hence, there is a need to find an alternative therapeutics against V. cholerae. Many herbal compounds present in nature having high medicinal value. From in-silico study, found two compound Luteolin from Tulsi and Catechin from Green Tea which showed good binding energy and druggish property. Abbreviations used: V. cholerae: Vibrio cholera, ADME: Absorption, digestion, metabolism and excretion, CT: Cholera toxin, TCP: Toxin co-regulated Pilus, GOLD: Genetic Optimization for Ligand Docking, Asp: Aspartic acid, Arg: Arginine, Lys: Lysine, Thr: Threonine, Tyr: Tyrosine, KEGG: Kyoto encyclopedia of Genes and Genomes.

Dataset Information

Toward antituberculosis drugs: in silico screening of synthetic compounds against Mycobacterium tuberculosisl,d-transpeptidase 2.

Publications

Toward antituberculosis drugs: in silico screening of synthetic compounds against Mycobacterium tuberculosisl,d-transpeptidase 2.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets