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https://www.readbyqxmd.com/read/28428773/mutation-at-g103-of-mtbftsz-altered-their-sensitivity-to-coumarins
#1
Duggirala Sridevi, Karpagam U Sudhakar, Ragamanvitha Ananthathatmula, Rakesh P Nankar, Mukesh Doble
Coumarins are natural polyphenol lactones comprising of fused rings of benzene and α-pyrone. The current study demonstrates the inhibitory effect of coumarins with various substitutions on Mycobacterium smegmatis mc(2) 155. We also demonstrate the effect of pomegranate (Punica granatum) extract containing ellagic acid, on M. smegmatis as well as their affect on MtbFtsZ (FtsZ from Mycobacterium tuberculosis). The ellagic acid extracts from pomegranate peels inhibit mycobacteria with a MIC of 25 μM and 0.3 to 3...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28423019/design-synthesis-and-structure-activity-relationship-study-of-wollamide-b-a-new-potential-anti-tb-agent
#2
Henok Asfaw, Katja Laqua, Anna Maria Walkowska, Fraser Cunningham, Maria Santos Martinez-Martinez, Juan Carlos Cuevas-Zurita, Lluís Ballell-Pages, Peter Imming
Wollamide B is a cationic antimycobacterial cyclohexapeptide that exhibits activity against Mycobacterium bovis (M. bovis) (IC50 of 3.1 μM). Aiming to define its structural activity relationship (SAR), optimizing potency and pharmacokinetic properties, libraries of analogues were synthesized following a standard Fmoc-based solid phase peptide synthesis approach. The antimycobacterial activities of wollamide B and all the synthesized analogues were tested against Mycobacterium tuberculosis (Mtb) H37Rv. Parallely, in vitro drug metabolism and pharmacokinetic (ADME) profiling was done for the synthesized compounds to evaluate their drug likeness...
2017: PloS One
https://www.readbyqxmd.com/read/28416541/efflux-attenuates-the-anti-bacterial-activity-of-q203-in-mycobacterium-tuberculosis
#3
Jichan Jang, Ryangyeo Kim, Minjeong Woo, Jinsun Jeong, Da Eun Park, Guehye Kim, Vincent Delorme
New and improved treatments for tuberculosis (TB) are urgently needed. Recently, it has been demonstrated that verapamil, an efflux inhibitor, can reduce bacterial drug tolerance caused by efflux pump activity when administered in combination with available anti-tuberculosis agents. The aim of this study was to evaluate the effectiveness of verapamil in combination with the anti-tuberculosis drug candidate Q203, which has recently been developed and is currently under clinical trials as a potential anti-tuberculosis agent...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28392458/anti-inflammatory-antimycobacterial-and-genotoxic-evaluation-of-doliocarpus-dentatus
#4
Raissa Borges Ishikawa, Maicon Matos Leitão, Roberto Mikio Kassuya, Luis Fernando Macorini, Flora Martinez Figueira Moreira, Claudia Andrea Lima Cardoso, Roberta Gomes Coelho, Arnildo Pott, Guilherme Martins Gelfuso, Julio Croda, Rodrigo Juliano Oliveira, Candida Aparecida Leite Kassuya
ETHNOPHARMACOLOGICAL RELEVANCE: Doliocarpus dentatus is a medicinal plant widely used in Mato Grosso do Sul State for removing the swelling pain caused by the inflammation process and for treating urine retention. AIM OF THE STUDY: The genotoxic aspects and the anti-inflammatory and antimycobacterial activity of the ethanolic extract obtained from the leaves of D. dentatus (EEDd) were investigated. MATERIALS AND METHODS: The EEDd was evaluated against Mycobacterium tuberculosis, and the compound composition was evaluated and identified by nuclear magnetic resonance (NMR)...
April 6, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28390957/isoniazid-derivatives-and-their-anti-tubercular-activity
#5
REVIEW
Yuan-Qiang Hu, Shu Zhang, Feng Zhao, Chuan Gao, Lian-Shun Feng, Zao-Sheng Lv, Zhi Xu, Xiang Wu
Tuberculosis (TB), which has been a scourge of humanity for thousands of years, is a worldwide pandemic disease caused mainly by Mycobacterium tuberculosis (MTB). The emergence of drug-resistant TB (DR-TB), multidrug-resistant TB (MDR-TB), extensively drug-resistant TB (XDR-TB) and totally drug-resistant TB (TDR-TB) increase the challenges to eliminate TB worldwide. Isoniazid (INH), a critical frontline anti-TB drug, is one of the most effective drugs used to treatment of TB infection for more than 60 years...
April 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28387444/comparative-modulation-of-levels-of-oxidative-stress-in-the-liver-of-anti-tuberculosis-drug-treated-wistar-rats-by-vitamin-b12-beta-carotene-and-spirulina-fusiformis-role-of-nf-kb-inos-il-6-and-il-10
#6
Sherry Joseph Martin, Evan Prince Sabina
PURPOSE: Isoniazid (INH) and Rifampicin (RIF) are known hepatotoxic agents. We compared the efficacy of Spirulina fusiformis and its active components vitamin B12 and beta-carotene in attenuating INH & RIF induced hepatotoxicity. We also tried to elucidate the inflammatory mechanism behind anti-tuberculosis drug induced hepatotoxicity. METHODS: INH & RIF were administered to Wistar albino rats for 28 days to induce hepatotoxicity. Spirulina fusiformis, vitamin B12 and beta-carotene were co-administered with INH & RIF and their hepatoprotective, antioxidant and immunomodulatory roles were studied through blood and liver analysis...
April 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28387179/chemotherapy-of-tuberculosis
#7
Thomas E Dobbs, Risa M Webb
The management of tuberculosis (TB) can be a challenging process that has implications both for the affected patient and public health. Effective anti-TB chemotherapy both cures and renders the patient noncontagious. Biological factors specific to M. tuberculosis necessitate the use of multiple drugs for prolonged durations to adequately eradicate infection. Recommended regimens address the complexities of eliminating organisms from diverse reservoirs while preventing the emergence of drug resistance. First-line anti-TB therapy for drug susceptible disease effectively cures almost all patients within 6-9 months...
April 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28384925/sle-and-tuberculosis-a-case-series-and-review-of-literature
#8
Prasanta Kumar Bhattacharya, Md Jamil, Aakash Roy, Kishore Kumar Talukdar
Systemic Lupus Erythematosus (SLE) and Tuberculosis (TB) are intricately related with an increase in the risk of TB in SLE. Primary mechanisms pertaining to the increased susceptibility for TB are the inherent immunodeficient state of SLE and use of immunosuppressant agents in the treatment of SLE. We report a case series of five female patients of SLE with TB who presented between January 2015 and December 2015 in a tertiary care teaching hospital in North Eastern India. All the patients were young to middle aged females having SLE with or without lupus nephritis who were on immunosuppressive therapy with corticosteroids, mycophenolate mofetil or cyclophosphamide...
February 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28380256/investigation-of-the-mycobacterial-enzyme-hsad-as-a-potential-novel-target-for-anti-tubercular-agents-using-a-fragment-based-drug-design-approach
#9
Ali Ryan, Elena Polycarpou, Nathan A Lack, Dimitrios Evangelopoulos, Christian Sieg, Alice Halman, Sanjib Bhakta, Olga Eleftheriadou, Timothy D McHugh, Sebastian Keany, Edward D Lowe, Romain Ballet, Areej Abuhammad, William R Jacobs, Alessio Ciulli, Edith Sim
BACKGROUND AND PURPOSE: With the emergence of extensively drug-resistant tuberculosis there is a need for new anti-tubercular drugs that work through novel mechanisms of action. The meta cleavage product hydrolase, HsaD, has been demonstrated to be critical to the survival of Mycobacterium tuberculosis in macrophages and is encoded in an operon involved in cholesterol catabolism, which is identical in M. tuberculosis and M. bovis BCG. EXPERIMENTAL APPROACH: We generated a mutant strain of M...
April 5, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28372908/novel-quinoxalinyl-chalcone-hybrid-scaffolds-as-enoyl-acp-reductase-inhibitors-synthesis-molecular-docking-and-biological-evaluation
#10
Vidya Desai, Sulaksha Desai, Sonia Naik Gaonkar, Uddesh Palyekar, Shrinivas D Joshi, Sheshagiri K Dixit
We report herein, first ever synthesis of series of novel differently substituted quinoxalinyl chalcones using Claisen Schmidt condensation, its molecular docking studies, and potential to be good anti-microbial, anti-tubercular and anti-cancer agents. The antimicrobial studies were carried out against Staphylococcus aureus, Escherichia coli and Candida albicans using disc diffusion procedure. The selected chalcones were tested for anti-cancer and cytotoxicity activity against MCF-7 cancer cell line using MTT assay method...
March 24, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28360859/dexamethasone-pretreatment-alleviates-isoniazid-lipopolysaccharide-hepatotoxicity-inhibition-of-inflammatory-and-oxidative-stress
#11
Hozeifa M Hassan, Hongli Guo, Bashir A Yousef, Ding Ping-Ping, Luyong Zhang, Zhenzhou Jiang
Isoniazid (INH) remains a cornerstone key constitute of the current tuberculosis management strategy, but its hepatotoxic potentiality remains a significant clinical problem. Our previous findings succeed to establish a rat model of INH hepatotoxicity employing the inflammatory stress theory in which non-injurious doses of inflammatory-mediating agent bacterial lipopolysaccharides (LPS) augmented the toxicity of INH that assist to uncover the mechanisms behind INH hepatotoxicity. Following LPS exposure, several inflammatory cells are activated and it is likely that the consequences of this activation rather than direct hepatocellular effects of LPS underlie the ability of LPS to augment toxic responses...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28357183/tuberculosis-and-guillain-barre-syndrome-a-chance-association
#12
Srikant Mohta, Manish Soneja, Surabhi Vyas, Wasim Khot
An 18-year-old boy presented with acute-onset quadriparesis that had developed 4 weeks prior. He had an intermittent fever and significant weight loss during this period. After extensive investigations, the patient was diagnosed with an acute motor and sensory axonal neuropathy (AMSAN) variant of Guillain-Barre syndrome (GBS) and disseminated tuberculosis with mediastinal lymphadenopathy, pericarditis, and pleural effusion. Plasmapheresis was performed and first-line anti-tubercular therapy was administered...
February 2017: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/28342755/mutation-analysis-of-the-interactions-between-mycobacterium-tuberculosis-caseinolytic-protease-c1-clpc1-and-ecumicin
#13
In-Pil Jung, Na-Reum Ha, A-Ru Kim, Sang-Heon Kim, Moon-Young Yoon
Ecumicin is a well-known and potent inhibitor of Mycobacterium tuberculosis. Although the target of ecumicin is caseinolytic protease C1 (ClpC1), the exact mechanism by which ecumicin inhibits ClpC1 has not been identified. To analyze ecumicin's action on ClpC1, site-directed mutagenesis was performed on its binding site. The estimated binding residues within ClpC1 to ecumicin were selected via in silico analysis using molecular docking. The selected residues were mutated by site-directed mutagenesis and the effects on ecumicin binding were analyzed...
March 22, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28333284/revisiting-the-mutant-prevention-concentration-to-guide-dosing-in-childhood-tuberculosis
#14
Devan Jaganath, H Simon Schaaf, Peter R Donald
The mutant prevention concentration (MPC) is a well-known concept in the chemotherapy of many bacterial infections, but is seldom considered in relation to tuberculosis (TB) treatment, as the required concentrations are generally viewed as unachievable without undue toxicity. Early studies revealed single mutations conferring high MICs of first- and second-line anti-TB agents; however, the growing application of genomics and quantitative drug susceptibility testing in TB suggests a wide range of MICs often determined by specific mutations and strain type...
March 9, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28318613/latent-tuberculosis-infection-screening-prior-to-biological-treatment-in-tunisian-patients
#15
Marwa Slouma, Ines Mahmoud, Olfa Saidane, Selma Bouden, Leila Abdelmoula
OBJECTIVES: The screening of latent tuberculosis infection (LTBI) is necessary to prevent infection in patients with chronic inflammatory disease (CID) undergoing biological treatment. We aimed to assess the efficacy of LTBI screening prior to biological treatment in Tunisia, considered as a high-incidence area of active TB disease. METHODS: We conducted a retrospective study over a period of 8 years [2007-2014] including patients with chronic inflammatory rheumatism receiving biologic agents since at least 6 months...
February 24, 2017: Thérapie
https://www.readbyqxmd.com/read/28317798/nontuberculous-mycobacterial-species-and-mycobacterium-tuberculosis-complex-coinfection-in-patients-with-pulmonary-tuberculosis-in-dr-soetomo-hospital-surabaya-indonesia
#16
Ni Made Mertaniasih, Deby Kusumaningrum, Eko Budi Koendhori, Tutik Kusmiati, Desak Nyoman Surya Suameitria Dewi
OBJECTIVE/BACKGROUND: The aim of this study was to analyze the detection of nontuberculous mycobacterial (NTM) species derived from sputum specimens of pulmonary tuberculosis (TB) suspects. Increasing prevalence and incidence of pulmonary infection by NTM species have widely been reported in several countries with geographical variation. MATERIALS AND METHODS: Between January 2014 and September 2015, sputum specimens from chronic pulmonary TB suspect patients were analyzed...
January 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28317629/mycobacterium-kansasii-infection-in-a-patient-receiving-biologic-therapy-not-all-reactive-interferon-gamma-release-assays-are-tuberculosis
#17
Nasir Saleem, Raya Saba, Srikanth Maddika, Mitchell Weinstein
Mycobacterium kansasii, a nontuberculous mycobacterium, can lead to lung disease similar to tuberculosis. Immunotherapeutic biologic agents predispose to infections with mycobacteria, including M kansasii. T-cell-mediated interferon gamma release assays like QuantiFERON-TB Gold Test (QFT) are widely used by clinicians for the diagnosis of infections with Mycobacterium tuberculosis; however, QFT may also show positive result with certain nontuberculous mycobacterial infections. We report a case of M kansasii pulmonary infection, with a positive QFT, in an immunocompromised patient receiving prednisone, leflunomide and tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody...
April 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28303436/mutations-in-catalase-peroxidase-katg-from-isoniazid-resistant-mycobacterium-tuberculosis-clinical-isolates-insights-from-molecular-dynamics-simulations
#18
Arethusa Lobo Pimentel, Regiane Bertin de Lima Scodro, Katiany Rizzieri Caleffi-Ferracioli, Vera Lúcia Dias Siqueira, Paula Aline Zanetti Campanerut-Sá, Luciana Dias Ghiraldi Lopes, Aryadne Larissa de Almeida, Rosilene Fressatti Cardoso, Flavio Augusto Vicente Seixas
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 ...
April 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28297677/recombinant-bcg-expressing-esx-1-of-mycobacterium-marinum-combines-low-virulence-with-cytosolic-immune-signaling-and-improved-tb-protection
#19
Matthias I Gröschel, Fadel Sayes, Sung Jae Shin, Wafa Frigui, Alexandre Pawlik, Mickael Orgeur, Robin Canetti, Nadine Honoré, Roxane Simeone, Tjip S van der Werf, Wilbert Bitter, Sang-Nae Cho, Laleh Majlessi, Roland Brosch
Recent insights into the mechanisms by which Mycobacterium tuberculosis, the etiologic agent of human tuberculosis, is recognized by cytosolic nucleotide sensors have opened new avenues for rational vaccine design. The only licensed anti-tuberculosis vaccine, Mycobacterium bovis BCG, provides limited protection. A feature of BCG is the partial deletion of the ESX-1 type VII secretion system, which governs phagosomal rupture and cytosolic pattern recognition, key intracellular phenotypes linked to increased immune signaling...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28287416/novel-pharmacological-activity-of-artesunate-and-artemisinin-their-potential-as-anti-tubercular-agents
#20
Won Hyung Choi
Tuberculosis is a major infectious disease that globally causes the highest human mortality. From this aspect, this study was carried out to evaluate novel pharmacological activities/effects of artesunate and artemisinin causing anti-tubercular activity/effects against Mycobacterium tuberculosis (Mtb). The anti-Mtb activities/effects of artesunate and artemisinin were evaluated using different anti-Mtb indicator assays, such as the resazurin microtiter assay, the Mycobacteria Growth Indicator Tube (MGIT) 960 system assay, and the Ogawa slant medium assay, as well as in vivo tests...
March 10, 2017: Journal of Clinical Medicine
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