Isoniazid-N-acylhydrazones as promising compounds for the anti-tuberculosis treatment.

Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis complex, still presents significant numbers of incidence and mortality, in addition to several cases of drug resistance. Resistance, especially to isoniazid, which is one of the main drugs used in the treatment, has increased. In this context, N-acylhydrazones derived from isoniazid have shown important anti-Mycobacterium tuberculosis activity.

Polymyxin B Activity Rescue by (-)-Camphene-Based Thiosemicarbazide Against Carbapenem-Resistant .

Due to the significant shortage of therapeutic options for carbapenem-resistant (CRE) infections, new drugs or therapeutic combinations are urgently required. We show in this study that (-)-camphene-based thiosemicarbazide (TSC) may act synergistically with polymyxin B (PMB) against CRE, rescuing the activity of this antimicrobial. With the specific aim of a better molecular understanding of this effect caused by the presence of TSC, theoretical calculations were also performed in this study.

Binding of piperine to mycobacterial RNA polymerase improves the efficacy of rifampicin activity against and nontuberculous mycobacteria.

Piperine (PPN) is a known inhibitor of efflux pumps in and synergism with rifampicin (RIF) has been proven. The current study evaluates the activity of PPN and synergism with RIF in rapidly and slowly growing nontuberculous mycobacteria (NTM). Also, to propose a possible mechanism of interaction of PPN with (Mlp) RNA polymerase (RNAp).

PanB over-representation as part of pyrazinamide action: a proteomic insight.

Pyrazinamide (PZA) represents a milestone as a first-line antituberculosis drug due to its sterilizing activity against . The protein changes induced by subinhibitory PZA exposure of in acidic pH were evaluated by a proteomic approach. Among the 1059 proteins identified, the specific acidification in the culture medium induced the over-representation of MurF (Rv2157c), and its under-representation was induced by 12 h of PZA exposure.

The chemistry of (Less.) H. Rob. flowers and its antimicrobial activities.

Twenty-one known specialised metabolites were isolated from the flowers of (Less.) H. Rob.

and Evaluations of Anti- Activity of Benzohydrazones Compounds.

Tuberculosis is a disease caused by , with high mortality rates and an extended treatment that causes severe adverse effects, besides the emergence of resistant bacteria. Therefore, the search for new compounds with anti- activity has considerably increased in recent years. In this context, benzohydrazones are significant compounds that have antifungal and antibacterial action.

Antituberculosis Activities of Lapachol and β-Lapachone in Combination with Other Drugs in Acidic pH.

The treatment of multidrug-resistant tuberculosis (MDR-TB) is a challenge to be overcome. The increase of resistant isolates associated with serious side effects during therapy leads to the search for substances that have anti-TB activity, which make treatment less toxic, and also act in the macrophage acidic environment promoted by the infection. The aim of this study was to investigate lapachol and β-lapachone activities in combination with other drugs against at neutral and acidic pH and its cytotoxicity.

Insight about cell wall remodulation triggered by rifampicin in Mycobacterium tuberculosis.

Rifampicin plays an important role during the treatment of tuberculosis, which makes it to be recommended throughout the regimen. The molecular target for rifampicin activity and resistance is the bacterial RNA polymerase coded by rpoB. However, it has been observed that Mycobacterium tuberculosis could use different metabolic pathways contributing to drug activity/resistance.

Minimum Bactericidal Concentration Techniques in : A Systematic Review.

Minimum bactericidal concentration (MBC) assay is an accepted parameter for evaluating new antimicrobial agents, and it is frequently used as a research tool to provide a prediction of bacterial eradication. To the best of our knowledge, there is no standardization among researchers regarding the technique used to detect a drug's MBC in . Thus, the aim of this systematic review is to discuss the available literature in determining a drug's MBC in , to find the most commonly used technique and standardize the process.

Possible Binding of Piperine in Mycobacterium tuberculosis RNA Polymerase and Rifampin Synergism.

The activity of rifampin (RIF) and piperine was evaluated at the relative transcript levels of 12 efflux pumps (EPs), and an additional mechanism was proposed to be behind the synergic interactions of piperine plus RIF in AutoDock v4.2.3 and Molegro v6 programs were used to evaluate PIP binding in RNA polymerase (RNAP).

Anti-Mycobacterium tuberculosis activity of essential oil and 6,7-dehydroroyleanone isolated from leaves of Tetradenia riparia (Hochst.) Codd (Lamiaceae).

Background: The global resurgence of tuberculosis (TB) and the development of drug resistance, as multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis isolates, are a threat to TB control and have created a need for new and more effective anti-TB drugs.

Aim: The current study evaluated the in vitro cytotoxicity and activity of Tetradenia riparia essential oil (TrEO) and 6,7-dehydroroyleanone pure compound against M. tuberculosis HRv and susceptible and resistant clinical isolates.

Promising Antituberculosis Activity of Piperine Combined with Antimicrobials: A Systematic Review.

Piperine, a bioactive compound from Piper nigrum and Piper longum, has shown promising activity as efflux pump (EP) inhibitor and as adjunct in treatment of tuberculosis (TB). The present systematic review investigated scientific studies of the activity of piperine against mycobacteria, with a focus on its mechanism of action, drug interactions, and antimycobacterial activity. A broad and rigorous literature search of three electronic databases (PubMed, Web of Knowledge, and LILACS) was performed according to the PRISMA statement.

Combinatory activity of linezolid and levofloxacin with antituberculosis drugs in Mycobacterium tuberculosis.

Setting: The increase of multidrug and extensively drug resistant Mycobacterium tuberculosis strains turns the search for new tuberculosis (TB) treatment options of paramount importance.

Objective: In this sense, the present study evaluates the in vitro activity of isoniazid (INH)/rifampicin (RIF)/levofloxacin (LVX) and INH/RIF/linezolid (LNZ) combinations in resistant M. tuberculosis.

In vitro combinatory activity of piperine and anti-tuberculosis drugs in Mycobacterium tuberculosis.

Tuberculosis (TB) is an important public health problem worldwide and the emergence of multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB worsened the global context. The resistance in Mycobacterium tuberculosis, the causative agent of TB, can partially derive from efflux pumps (EPs) activity in plasma membrane. Due to the recent discovery of piperine (PIP), an organic alkaloid compound, increasing the bioavailability of various drugs, the current assay evaluated the combined activity of PIP and anti-TB drugs in susceptible and resistant M.

RDMycobacterium tuberculosis lineage in the Brazil/Paraguay/Argentina triple border.

The high tuberculosis (TB) incidence rates, the closeness of the cities and the high migration flux on the Brazil/Paraguay/Argentina border deserves an in-depth study, using Mycobacterial Interspersed Repetitive Unit (MIRU) and Spoligotyping genetic markers to explore the impact of the Mycobacterium tuberculosis RD lineage on disease transmission and resistance to anti-TB drugs in this setting. Although without the totality of M. tuberculosis isolates causing TB in this studied setting, a number of 97 isolates obtained from sputa samples culture of patients with confirmed TB, from 2013 to 2015, were submitted to 24 loci MIRU, Spoligotyping, detection of RD lineage and detection of mutation related to isoniazid and rifampicin resistance by MTBDRplus/DNA STRIP.

Intramacrophage Mycobacterium tuberculosis efflux pump gene regulation after rifampicin and verapamil exposure.

Objectives: Since resistance of Mycobacterium tuberculosis (Mtb) partially derives from efflux pumps (EPs) in the plasma membrane, the current study evaluates EPs in Mtb exposed to rifampicin in the presence of the EP inhibitor verapamil, within a macrophage environment.

Methods: Human acute monocytic leukaemia cell line THP-1 was infected with Mtb H37Rv and exposed to rifampicin and verapamil alone and in combination for 24 and 72 h. After RNA extraction, quantitative PCR was carried out for 11 EP genes using SYBR green PCR master mix in the StepOne™ Real-Time PCR System.

New insights on Ethambutol Targets in Mycobacterium tuberculosis.

Background: In recent years, very few effective drugs against Mycobacterium tuberculosis have emerged, which motivates the research with drugs already used in the treatment of tuberculosis. Ethambutol is a bacteriostatic drug that affects cell wall integrity, but the effects of this drug on bacilli are not fully exploited.

Objective: Based on the need to better investigate the complex mechanism of action of ethambutol, our study presented the proteome profile of M.

Antimicrobial and Antioxidant Activities of the Extract and Fractions of Tetradenia riparia (Hochst.) Codd (Lamiaceae) Leaves from Brazil.

Tetradenia riparia (Lamiaceae) is native to Central Africa popularly known as myrrh, used in folk medicine to treat various diseases like malaria, gastroenteritis, and tropical skin disease. This research was to evaluate the antioxidant and antibacterial activities of the crude extract (CE) and fractions (FR) of the T. riparia by classical chromatography.

Systematic review on the proteomic profile of Mycobacterium tuberculosis exposed to drugs.

The authors present an overview about proteomics studies in Mycobacterium tuberculosis exposed to some anti-tuberculosis drugs and new candidates, using two-dimensional gel electrophoresis and mass spectrometry. To date, that the authors have knowledge, this is the first studies that was performed specifically in M. tuberculosis using systematic review on electronic literature conducted in three databases using the following search terms: tuberculosis OR mycobacterium tuberculosis, proteome OR proteomics, and mass spectrometry electrospray ionization OR matrix-assisted laser desorption ionization OR two-dimensional gel electrophoresis.

Activity of rifampicin and linezolid combination in Mycobacterium tuberculosis.

Background: Linezolid (LZD) is not commonly used for treating tuberculosis (TB), but in some patients with drug-resistant TB it is being used. However, the in vitro LZD activity, in combination with rifampicin (RIF) against Mycobacterium tuberculosis has not been fully elucidated.

Aims: The aim of this study was to evaluate the in vitro activity of RIF/LZD combination against M.

Mutations in catalase-peroxidase KatG from isoniazid resistant Mycobacterium tuberculosis clinical isolates: insights from molecular dynamics simulations.

The current multidrug therapy for tuberculosis (TB) is based on the use of isoniazid (INH) in combination with other antibiotics such as rifampin, ethambutol and pyrazinamide. Literature reports have shown that Mycobacterium tuberculosis, the causative agent of TB, has become resistant to this treatment by means of point mutations in the target enzymes of these drugs, such as catalase-peroxidase (KatG). By means of equilibrium molecular dynamics in the presence of the ligand, this work evaluated ten point mutations described in the enzyme KatG that are related to resistance to INH .

Morphological changes and differentially expressed efflux pump genes in Mycobacterium tuberculosis exposed to a rifampicin and verapamil combination.

The aim of the present study was to (i) evaluate the in vitro action of rifampicin (RIF), ethambutol or isoniazid with efflux pumps inhibitors (EPIs) in Mycobacterium tuberculosis (Mtb) H37Rv and (ii) evaluate the morphological and efflux pumps (EPs) transcriptional changes by the action of rifampicin + verapamil combination (RIF + VP). The minimal inhibitory concentration and synergic effect of drug combinations were determined by Resazurin Microtiter Plate Assay and Resazurin Drugs Combination Microtiter Assay, respectively. VP showed greater capacity of ethidium bromide accumulation and RIF + VP had the lower fractional inhibitory concentration index.