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.

Rescue of susceptibility to second-line drugs in resistant clinical isolates of .

Antibiotic resistance is one of the biggest threats to global health, and this study aimed better understand how the efflux pumps are related to this process in tuberculosis clinical isolates. The combination of antibiotics plus efflux pumps (EP) inhibitors was able to restore the susceptibility of clinical isolates in 100% of aminoglycosides resistance and 33.3% of the fluoroquinolones resistance.

3,5-dinitrobenzoylhydrazone derivatives as a scaffold for antituberculosis drug development.

The development of drugs is essential to eradicate tuberculosis. Sixteen 3,5-dinitrobenzoylhydrazone () derivatives and their synthetic precursors 3,5-dinitrobenzoylhydrazide () and methyl ester () were screened for their anti- () potential. Twelve compounds had minimum inhibitory concentration (MIC) ranging from 0.

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.

Speech-brain phase coupling is enhanced in low contextual semantic predictability conditions.

Semantic prediction and cortical entrainment to the acoustic landmarks of the speech envelope are two fundamental yet qualitatively different mechanisms that facilitate speech comprehension. However, it is not clear how and to what extent those mechanisms interact with each other. On the one hand, richer semantic context could enhance the perceptual representation of a predictable stimulus, thus improving speech entrainment.

The 20S proteasome activator PA28γ controls the compaction of chromatin.

PA28γ (also known as PSME3), a nuclear activator of the 20S proteasome, is involved in the degradation of several proteins regulating cell growth and proliferation and in the dynamics of various nuclear bodies, but its precise cellular functions remain unclear. Here, using a quantitative FLIM-FRET based microscopy assay monitoring close proximity between nucleosomes in living human cells, we show that PA28γ controls chromatin compaction. We find that its depletion induces a decompaction of pericentromeric heterochromatin, which is similar to what is observed upon the knockdown of HP1β (also known as CBX1), a key factor of the heterochromatin structure.

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.

(-)-Camphene-based derivatives as potential antibacterial agents against and spp.

To evaluate the activity of (-)-camphene-based thiosemicarbazide (TSC) and 4-hydroxy-thiosemicarbazone (4-OH-TSZ), alone and in combination against Gram-positive. MIC were determined for , spp. reference strains and clinical isolates.

Synthesis and biological evaluation of 12 novel (-)-camphene-based 1,3,4-thiadiazoles against .

To evaluate the activity, cytotoxicity and efflux pumps inhibition of a series of 12 novels (-)-camphene-based 1,3,4-thiadiazoles (TDZs) against (). The minimum inhibitory concentration (MIC), cytotoxicity for three cell lines, ethidium bromide accumulation and checkerboard methods were carried out. Compounds (, , , , and ) showed significant anti- activity (MIC 3.

Synthesis and anti-Mycobacterium tuberculosis activity of imide-β-carboline and carbomethoxy-β-carboline derivatives.

A series of methyl β-carboline carboxylates (2a-g) and of imide-β-carboline derivatives containing the phthalimide (4a-g), maleimide (5b, g) and succinimide (6b, e, g) moiety were synthesized, and evaluated for their activity against Mycobacterium tuberculosis HRv. The most active β-carboline derivatives against the reference strain were assayed for their cytotoxicity and the activity against resistant M. tuberculosis clinical isolates.

Activity of (-)-Camphene Derivatives Against Mycobacterium tuberculosis in Acidic pH.

Background: For more than 60 years, the lack of new anti-tuberculosis drugs and the increase of resistant Mycobacterium tuberculosis lineages exhibit a therapeutic challenge, demanding new options for the treatment of resistant tuberculosis.

Objective: Herein, we determined the (i) activities of (-)-camphene and its derivatives and (ii) combinatory effect with pyrazinamide (PZA) against Mycobacterium tuberculosis in acidic pH and (iii) cytotoxicity on VERO cells.

Methods: The activity of (-)-camphene and its 15 derivatives was determined in M.

Hydrazone, benzohydrazones and isoniazid-acylhydrazones as potential antituberculosis agents.

To evaluate the potential of three benzohydrazones (-), four acylhydrazones derived from isoniazid (INH-acylhydrazones) (-) and one hydrazone () as antituberculosis agents. Inhibitory and bactericidal activities were determined for the reference () strain and clinical isolates. Cytotoxicity, drug combinations and ethidium bromide accumulation assays were also performed.

Ginger essential oil and fractions against Mycobacterium spp.

Ethnopharmacological Relevance: Zingiber officinale (ginger) is a perennial herbaceous plant native in tropical Asia and generally cultivated in most American tropical countries with widespread use in popular medicine. Ginger essential oil (GEO) has been reported to exhibit several biological activities, such as antimicrobial.

Aims Of The Study: The aim of this study was to determine the composition and the property of GEO and related fractions against Mtb and NTM, as well as their cytotoxicity.

Eugenol and derivatives activity against Mycobacterium tuberculosis, nontuberculous mycobacteria and other bacteria.

Aim: To evaluate (i) the in vitro activity of eugenol (EUG) and three derivatives against Mycobacterium tuberculosis (Mtb), nontuberculous mycobacteria (NTM) and other bacteria, (ii) the EUG and antituberculosis drugs combinatory effect and (iii) the EUG and its derivatives cytotoxicity.

Materials & Methods: Minimum inhibitory concentration of the compounds were determined by resazurin microtiter or broth microdilution assay and the drug interaction between EUG and antituberculosis drugs by resazurin drug combination microtiter. The cytotoxicity was carried out in macrophages, HeLa and VERO cells.

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.

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.

PIP30/FAM192A is a novel regulator of the nuclear proteasome activator PA28γ.

PA28γ is a nuclear activator of the 20S proteasome involved in the regulation of several essential cellular processes, such as cell proliferation, apoptosis, nuclear dynamics, and cellular stress response. Unlike the 19S regulator of the proteasome, which specifically recognizes ubiquitylated proteins, PA28γ promotes the degradation of several substrates by the proteasome in an ATP- and ubiquitin-independent manner. However, its exact mechanisms of action are unclear and likely involve additional partners that remain to be identified.

Carvacrol activity & morphological changes in Mycobacterium tuberculosis.

Aim: Evaluating carvacrol, derivatives and carvacrol plus anti-TB (anti-tuberculous) drug combination activities in Mycobacterium tuberculosis as well as carvacrol cytotoxicity, efflux pump inhibitor activity and morphological changes in M. tuberculosis HRv.

Methods: Carvacrol (CAR) and derivatives' activities were determined by resazurin microtiter assay and drug interaction by resazurin drug combination microtiter.

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.

The stability of Fbw7α in M-phase requires its phosphorylation by PKC.

Fbw7 is a tumor suppressor often deleted or mutated in human cancers. It serves as the substrate-recruiting subunit of a SCF ubiquitin ligase that targets numerous critical proteins for degradation, including oncoproteins and master transcription factors. Cyclin E was the first identified substrate of the SCFFbw7 ubiquitin ligase.