Anti-tubercular activity of some six membered heterocycle compounds

2019 ◽  
Author(s):  
Chem Int
Keyword(s):  
Infectious Disease ◽  
Cell Wall ◽  
Latent Tuberculosis ◽  
Drug Resistant ◽  
Significant Development ◽  
Tb Treatment ◽  
Modern Drug ◽  
Mycobacterial Cell Wall ◽  
Membered Heterocycle ◽  
New Chemical Entity

The effectiveness in TB treatment is difficult because the structural composition of the mycobacterial cell wall is very complicated, which makes many drugs ineffective. Tuberculosis is still one of the most imperative infectious disease worldwide becouse its important reason is drug resistant, persistent or latent tuberculosis and synergism with HIV. Furthermore no any new chemical entity has come. The recently application of modern drug design promise to bring significant development in the fight against TB. In present review we discussed brief introduction of tuberculosis.

scholarly journals Isoniazid Induces Apoptosis Of Activated CD4+ T Cells

2014 ◽  
Vol 289 (44) ◽  
pp. 30190-30195 ◽  
Author(s):  
Sultan Tousif ◽  
Dhiraj Kumar Singh ◽  
Shaheer Ahmad ◽  
Prashini Moodley ◽  
Maitree Bhattacharyya ◽  
...  
Keyword(s):  
Infectious Disease ◽  
T Cells ◽  
Immune Responses ◽  
Therapeutic Agents ◽  
Current Therapy ◽  
Drug Resistant ◽  
Tb Treatment ◽  
Short Course ◽  
Directly Observed Treatment ◽  
Immune Impairment

Tuberculosis (TB) remains the second highest killer from a single infectious disease worldwide. Current therapy of TB is lengthy and consists of multiple expensive antibiotics, in a strategy referred to as Directly Observed Treatment, Short Course (DOTS). Although this therapy is effective, it has serious disadvantages. These therapeutic agents are toxic and are associated with the development of a variety of drug-resistant TB strains. Furthermore, patients treated with DOTS exhibit enhanced post-treatment susceptibility to TB reactivation and reinfection, suggesting therapy-related immune impairment. Here we show that Isoniazid (INH) treatment dramatically reduces Mycobacterium tuberculosis antigen-specific immune responses, induces apoptosis in activated CD4+ T cells, and renders treated animals vulnerable to TB reactivation and reinfection. Consequently, our findings suggest that TB treatment is associated with immune impairment.

scholarly journals AN EXHAUSTIVE REVIEW ON EMERGING DRUG TARGETS OF TUBERCULOSIS WITH SPECIAL EMPHASIS ON CELL WALL SYNTHESIS

2021 ◽  
pp. 1-7
Author(s):  
SNEHAL R THAKAR ◽  
DEEPALI A BANSODE
Keyword(s):  
Cell Wall ◽  
Genetic Information ◽  
Drug Targets ◽  
Drug Candidate ◽  
Drug Resistant ◽  
Mortality And Morbidity ◽  
Mycobacterial Cell ◽  
Causes Of Mortality ◽  
Mycobacterial Cell Wall ◽  
Novel Drug

Tuberculosis (TB) is one of the top 10 causes of mortality and morbidity. Worldwide, yet, it has been over 60 years since a novel drug was introduced in market to treat the disease exclusively. Increased number of drug resistant TB cases has prompted the search for novel potent anti-TB drug. Mycobacterial cell wall has unique structure which provides integrity to the cell. The future development of new potent anti-TB drug targets is associated with the synthesis of various cell wall constituents; the structural and genetic information about mycobacterial cell wall envelope is now available. In the present review, we have focused on prospective drug targets that can be optimum triumph for successful drug candidate.

scholarly journals Mycobacterial Cell Wall: A Source of Successful Targets for Old and New Drugs

2020 ◽  
Vol 10 (7) ◽  
pp. 2278 ◽  
Author(s):  
Catherine Vilchèze
Keyword(s):  
Cell Wall ◽  
New Drugs ◽  
Wall Structure ◽  
Tb Treatment ◽  
Mycobacterial Cell ◽  
Short Course ◽  
Cell Wall Disruption ◽  
The Face ◽  
Mycobacterial Cell Wall ◽  
Wall Components

Eighty years after the introduction of the first antituberculosis (TB) drug, the treatment of drug-susceptible TB remains very cumbersome, requiring the use of four drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) for two months followed by four months on isoniazid and rifampicin. Two of the drugs used in this “short”-course, six-month chemotherapy, isoniazid and ethambutol, target the mycobacterial cell wall. Disruption of the cell wall structure can enhance the entry of other TB drugs, resulting in a more potent chemotherapy. More importantly, inhibition of cell wall components can lead to mycobacterial cell death. The complexity of the mycobacterial cell wall offers numerous opportunities to develop drugs to eradicate Mycobacterium tuberculosis, the causative agent of TB. In the past 20 years, researchers from industrial and academic laboratories have tested new molecules to find the best candidates that will change the face of TB treatment: drugs that will shorten TB treatment and be efficacious against active and latent, as well as drug-resistant TB. Two of these new TB drugs block components of the mycobacterial cell wall and have reached phase 3 clinical trial. This article reviews TB drugs targeting the mycobacterial cell wall in use clinically and those in clinical development.

The Global Landscape of Tuberculosis Therapeutics

2019 ◽  
Vol 70 (1) ◽  
pp. 105-120 ◽  
Author(s):  
Jeffrey A. Tornheim ◽  
Kelly E. Dooley
Keyword(s):  
Infectious Disease ◽  
Latent Infection ◽  
Treatment Options ◽  
Drug Resistant ◽  
Multidrug Therapy ◽  
Tb Treatment ◽  
Extensively Drug Resistant ◽  
Recent Advances ◽  
Development Pipeline ◽  
Near Term

Tuberculosis (TB) is one of the oldest infections afflicting humans yet remains the number one infectious disease killer worldwide. Despite decades of experience treating this disease, TB regimens require months of multidrug therapy, even for latent infections. There have been important recent advances in treatment options across the spectrum of TB, from latent infection to extensively drug-resistant (XDR) TB disease. In addition, new, potent drugs are emerging out of the development pipeline and are being tested in novel regimens in multiple currently enrolling trials. Shorter, safer regimens for many forms of TB are now available or are in our near-term vision. We review recent advances in TB therapeutics and provide an overview of the upcoming clinical trials landscape that will help define the future of worldwide TB treatment.

scholarly journals Long-term mortality and active TB disease among patients who were lost to follow-up during second line tuberculosis treatment in 2011-2014: population-based study in the country of Georgia

2021 ◽  
Author(s):  
Giorgi Kuchukhidze ◽  
Davit Baliashvili ◽  
Natalia Adamashvili ◽  
Ana Kasradze ◽  
Russell R Kempker ◽  
...  
Keyword(s):  
Multivariable Analysis ◽  
Positive Culture ◽  
Population Based ◽  
Drug Resistant ◽  
Second Line ◽  
Adjusted Risk ◽  
Tb Treatment ◽  
Country Of Georgia

Abstract BACKGROUND High rates of loss to follow-up (LFU) exist among patients with multi-drug and extensively drug-resistant tuberculosis (M/XDR TB); We aimed to identify long-term clinical outcomes of patients who were LFU during second-line TB treatment. METHODS We conducted a follow-up study among adults who received second-line TB treatment in the country of Georgia during 2011-2014 with a final outcome of LFU. We attempted to interview all LFU patients, administered a structured questionnaire and obtained sputum samples. Active TB at follow-up was defined by positive sputum Xpert-TB/RIF or culture. RESULTS Follow-up information was obtained for 461 patients, among these patients, 107 (23%) died and 177 (38%) were contacted, of those contacted 123 (69%) consented to participate and 92 provided sputum samples. Thirteen (14%) had active TB with an estimated infectious time-period for transmitting drug-resistant TB in the community of 480 days (IQR=803). In multivariable analysis, positive culture at the time of LFU was associated with active TB at the time of our study (adjusted risk ratio=13.3, 95% CI: 4.2, 42.2) CONCLUSIONS Nearly one-quarter of patients on second-line TB treatment who were LFU died. Among those LFU evaluated in our study, one in seven remained in the community with positive sputum cultures. To reduce death and transmission of disease, additional strategies are needed to encourage patients to complete treatment.

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