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https://www.readbyqxmd.com/read/29454849/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biological-therapies-an-infectious-diseases-perspective-intracellular-signaling-pathways-tyrosine-kinase-and-mtor-inhibitors
#1
REVIEW
Mark Reinwald, Jose T Silva, Nicolas J Mueller, Jesús Fortún, Christian Garzoni, Johan W de Fijter, Mario Fernández-Ruiz, Paolo Grossi, Jose María Aguado
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of therapies targeting different intracellular signaling pathways and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
February 15, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29453078/diterpenoids-from-the-roots-of-euphorbia-ebracteolata-and-their-anti-tuberculosis-effects
#2
Zhenlong Yu, Yunlong Wei, Xiangge Tian, Qiulong Yan, Qingsong Yan, Xiaokui Huo, Chao Wang, Chengpeng Sun, Baojing Zhang, Xiaochi Ma
Euphorbia ebracteolata was a natural medicine for the treatment of tuberculosis. The present work has performed the investigation of bioactive chemical substances from the roots of E. ebracteolata. Using various chromatographic techniques, 15 compounds were obtained from the roots of E. ebracteolata. On the basis of widely spectroscopic data analyses, the isolated compounds were determined to be diterpenoids, including rosane derivatives (1-12), isopimarane (13), abietane (14), and lathyrane (15), among which compounds 1-4, and 9 were undescribed previously...
February 12, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29447988/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biological-therapies-an-infectious-diseases-perspective-agents-targeting-lymphoid-cells-surface-antigens-i-cd19-cd20-and-cd52
#3
REVIEW
Małgorzata Mikulska, Simone Lanini, Carlota Gudiol, Lubos Drgona, Giuseppe Ippolito, Mario Fernández-Ruiz, Bernd Salzberger
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting CD19, CD20 and CD52 and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
February 12, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29447987/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biological-therapies-an-infectious-diseases-perspective-soluble-immune-effector-molecules-ii-agents-targeting-interleukins-immunoglobulins-and-complement
#4
REVIEW
Kevin L Winthrop, Xavier Mariette, Jose T Silva, Esther Benamu, Leonard H Calabrese, Alexandre Dumusc, Josef S Smolen, José María Aguado, Mario Fernández-Ruiz
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting interleukins, immunoglobulins and complement factors and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
February 12, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29441052/harnessing-the-mtor-pathway-for-tuberculosis-treatment
#5
REVIEW
Pooja Singh, Selvakumar Subbian
Tuberculosis (TB) remains as one of the leading killer infectious diseases of humans. At present, the standard therapeutic regimen to treat TB comprised of multiple antibiotics administered for a minimum of six months. Although these drugs are useful in controlling TB burden globally, they have not eliminated the disease. In addition, the lengthy duration of treatment with multiple drugs contributes to patient non-compliance that can result in the development of drug resistant strains (MDR and XDR) of Mycobacterium tuberculosis (Mtb), the causative agent of TB...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29407993/synthesis-of-coumarin-theophylline-hybrids-as-a-new-class-of-anti-tubercular-and-anti-microbial-agents
#6
Sumitra N Mangasuli, Kallappa M Hosamani, Hirihalli C Devarajegowda, Mahantesh M Kurjogi, Shrinivas D Joshi
A series of novel coumarin-theophylline hybrids were synthesized and examined for their anti-tubercular activity in vitro against Mycobacterium tuberculosis H37Rv, anti-microbial activity in vitro against gram-positive bacteria (Staphylococcus aureus) and gram-negative bacterias (Escherichia coli, Salmonella typhi) as well as fungi (Candida albicans). The compound (3a) has shown excellent anti-tubercular activity with MIC of 0.12 μg/mL. Electron donating compounds (3a, 3f) have displayed significant anti-microbial activity...
January 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29407980/fluoroquinolone-derivatives-and-their-anti-tubercular-activities
#7
Yi-Lei Fan, Jian-Bing Wu, Xiang-Wei Cheng, Feng-Zhi Zhang, Lian-Shun Feng
Tuberculosis (TB) remains one of the most widespread and leading deadliest diseases, around one-third of the world's population harbor a latent infection by Mycobacterium tuberculosis (MTB), and 5-10% eventually develop an active TB. The emergency of MTB new virulent forms as well as the co-infection between MTB and HIV alarming the serious problem in TB control and demanding the need for new drugs more potent than earlier with safe ADME profile. Fluoroquinolones are emerged as a large family of synthetic broad spectrum antibiotics, and some of them were recommended as the second-line agents for the treatment of TB mainly in cases involving resistance or intolerance to first-line anti-TB therapy by WHO...
January 31, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29407960/an-overview-on-crystal-structures-of-inha-protein-apo-form-in-complex-with-its-natural-ligands-and-inhibitors
#8
REVIEW
Aurélien Chollet, Laurent Maveyraud, Christian Lherbet, Vania Bernardes-Génisson
The enoyl-ACP reductase InhA from the mycobacterial fatty acid biosynthesis pathway has become a target of interest for the development of new anti-tubercular drugs. This protein has been identified as essential for the survival of Mycobacterium tuberculosis, the causative agent of tuberculosis, and as the main target of two pro-drugs: isoniazid, the frontline anti-tubercular drug, and ethionamide, a second-line medicine. Since most cases of resistance to isoniazid and ethionamide result from mutations in the mycobacterial activating enzyme (KatG for isoniazid and EthA for ethionamide), research of direct InhA inhibitors, avoiding the activation step, has emerged as a promising strategy for combating tuberculosis...
February 2, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29380185/intravitreal-dexamethasone-implant-as-an-option-for-anti-inflammatory-therapy-of-tuberculosis-uveitis
#9
Murat Hasanreisoglu, Gokcen Gulpinar Ikiz, Zeynep Aktas, Sengul Ozdek
INTRODUCTION: Tuberculosis-associated uveitis remains a diagnostic and therapeutic challenge. After diagnosis of tuberculosis and initiation of anti-tuberculosis therapy for tuberculosis uveitis, the clinical responses are favorable. However, at 4-6 weeks of the therapy, there commonly occurs paradoxical deterioration due to an increase in inflammation which is often accompanied by cystoid macular edema. Thus, adjuvant administration of anti-inflammatory regimen should be considered. For this purpose, systemic and periocular steroids, systemic and intravitreal immunosuppressive agents have been tested...
January 29, 2018: International Ophthalmology
https://www.readbyqxmd.com/read/29373690/novel-function-of-cyclooxygenase-2-suppressing-mycobacteria-by-promoting-autophagy-via-protein-kinase-b-mammalian-target-of-rapamycin-pathway
#10
Wenjing Xiong, Qian Wen, Xialin Du, Jinli Wang, Wenting He, Ruining Wang, Shengfeng Hu, Xinying Zhou, Jiahui Yang, Yuchi Gao, Li Ma
In Mycobacterium tuberculosis-infected macrophages, cyclooxygenase-2 (COX-2) expression considerably increases to defend the body against mycobacteria by regulating adaptive immunity and restoring the mitochondrial inner membrane. Moreover, in cancer cells, COX-2 enhances the autophagy machinery, an important bactericidal mechanism. However, the association between M. tuberculosis-induced COX-2 and autophagy-mediated anti-mycobacterial response has not been explored. Here, COX-2 expression silencing reduced the autophagy and bactericidal activity against intracellular M...
January 24, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29373270/reversed-isoniazids-design-synthesis-and-evaluation-against-mycobacterium-tuberculosis
#11
Malkeet Kumar, Kawaljit Singh, Andile H Ngwane, Fahreta Hamzabegovic, Getahun Abate, Bienyameen Baker, Ian Wiid, Daniel F Hoft, Peter Ruminski, Kelly Chibale
Novel reversed isoniazid (RINH) agents were synthesized by covalently linking isoniazid with various efflux pump inhibitor (EPI) cores and their structural motifs. These RINH agents were then evaluated for anti-mycobacterial activity against sensitive, isoniazid mono-resistant and MDR clinical isolates of M. tuberculosis and a selected number of compounds were also tested ex vivo for intracellular activity as well as in the ethidium bromide (EB) assay for efflux pump inhibition efficacy. The potency of some compounds against various strains of M...
December 29, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29372069/diagnosis-and-treatment-of-latent-tuberculosis-in-patients-with-multiple-sclerosis-expert-consensus-on-behalf-of-the-colombian-association-of-neurology-committee-of-multiple-sclerosis
#12
Carlos Navas, Carlos A Torres-Duque, Joe Munoz-Ceron, Carlos Álvarez, Juan R García, Luis Zarco, Lázaro A Vélez, Carlos Awad, Carlos Alberto Castro
Background: Multiple sclerosis is an inflammatory and neurodegenerative demyelinating disease. Current treatment of multiple sclerosis focuses on the use of immunomodulatory, immunosuppressant, and selective immunosuppressant agents. Some of these medications may result in high risk of opportunistic infections including tuberculosis. Objective: The purpose of this study was to obtain consensus from a panel of neurologists, pulmonologists, infectious disease specialists, and epidemiology experts regarding the diagnosis, treatment, and monitoring of latent tuberculosis in patients with multiple sclerosis...
January 2018: Multiple Sclerosis Journal—Experimental, Translational and Clinical
https://www.readbyqxmd.com/read/29363172/bcg-vaccination-drives-accumulation-and-effector-function-of-innate-lymphoid-cells-in-murine-lungs
#13
Pia Steigler, Naomi J Daniels, Tim R McCulloch, Brin M Ryder, Sarah K Sandford, Joanna R Kirman
The tuberculosis (TB) vaccine bacille Calmette-Guérin (BCG) prevents disseminated childhood TB, however fails to protect against the more prevalent pulmonary TB. Limited understanding of the immune response to Mycobacterium tuberculosis, the causative agent of TB, has hindered development of improved vaccines. Although memory CD4 T cells are considered the main mediators of protection against TB, recent studies suggest there are other key subsets that contribute to anti-mycobacterial immunity. To that end, innate cells may be involved in the protective response...
January 9, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29360989/evolution-of-drug-resistance-in-mycobacterium-tuberculosis-a-review-on-the-molecular-determinants-of-resistance-and-implications-for-personalized-care
#14
Navisha Dookie, Santhuri Rambaran, Nesri Padayatchi, Sharana Mahomed, Kogieleum Naidoo
Drug-resistant TB (DR-TB) remains a significant challenge in TB treatment and control programmes worldwide. Advances in sequencing technology have significantly increased our understanding of the mechanisms of resistance to anti-TB drugs. This review provides an update on advances in our understanding of drug resistance mechanisms to new, existing drugs and repurposed agents. Recent advances in WGS technology hold promise as a tool for rapid diagnosis and clinical management of TB. Although the standard approach to WGS of Mycobacterium tuberculosis is slow due to the requirement for organism culture, recent attempts to sequence directly from clinical specimens have improved the potential to diagnose and detect resistance within days...
January 19, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29358328/a-human-xenobiotic-nuclear-receptor-contributes-to-nonresponsiveness-of-mycobacterium-tuberculosis-to-the-antituberculosis-drug-rifampicin
#15
Ella Bhagyaraj, Drishti Tiwari, Nancy Ahuja, Ravikanth Nanduri, Ankita Saini, Rashi Kalra, Sumit Kumar, Ashok Kumar Janmeja, Pawan Gupta
Mycobacterium tuberculosis is the causative agent of tuberculosis (TB). It acquires phenotypic drug resistance inside macrophages, and this resistance mainly arises from host-induced stress. However, whether cellular drug efflux mechanisms in macrophages contribute to nonresponsiveness of M. tuberculosis to anti-TB drugs is unclear. Here, we report that xenobiotic nuclear receptors mediate TB drug nonresponsiveness by modulating drug efflux transporters in macrophages. This was evident from expression analysis of drug efflux transporters in macrophages isolated from TB patients...
January 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29348046/synthesis-of-sulfamide-analogues-of-deoxthymidine-monophosphate-as-potential-inhibitors-of-mycobacterial-cell-wall-biosynthesis
#16
Kajitha Suthagar, Wanting Jiao, Hélène Munier-Lehmann, Antony J Fairbanks
The recently discovered enzyme Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt), which catalyses the phosphorylation of deoxythymidine monophosphate (dTMP) to give deoxythymidine diphosphate (dTDP), is indispensable for the growth and survival of M. tuberculosis as it plays an essential role in DNA synthesis. Inhibition of TMPKmt is an attractive avenue for the development of novel anti-tuberculosis agents. Based on the premise that sulfamide may be a suitable isostere of phosphate, deoxythymidine analogues comprising various substituted sulfamides at C5' were modelled in silico into the active site of TMPKmt (PDB accession code: 1N5K) using induced-fit docking methods...
January 11, 2018: Carbohydrate Research
https://www.readbyqxmd.com/read/29322466/using-rt-qpcr-for-quantifying-mycobacteria-marinum-from-in%C3%A2-vitro-and-in-vivo-samples
#17
Han Xaio, Stephen H Gillespie
Mycobacterium marinum, the causative agent of fish tuberculosis, is rarely a human pathogen causing a chronic skin infection. It is now wildely used as a model system in animal models, especially in zebra fish model, to study the pathology of tuberculosis and as a means of screening new anti-tuberculosis agent. To facilitate such research, quantifying the viable count of M. marinum bacteria is a crucial step. The main approach used currently is still by counting the number of colony forming units (cfu), a method that has been in place for almost 100 years...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29321020/meta-analysis-of-human-gene-expression-in-response-to-mycobacterium-tuberculosis-infection-reveals-potential-therapeutic-targets
#18
Zhang Wang, Seda Arat, Michal Magid-Slav, James R Brown
BACKGROUND: With the global emergence of multi-drug resistant strains of Mycobacterium tuberculosis, new strategies to treat tuberculosis are urgently needed such as therapeutics targeting potential human host factors. RESULTS: Here we performed a statistical meta-analysis of human gene expression in response to both latent and active pulmonary tuberculosis infections from nine published datasets. We found 1655 genes that were significantly differentially expressed during active tuberculosis infection...
January 10, 2018: BMC Systems Biology
https://www.readbyqxmd.com/read/29297425/extensively-drug-resistant-tuberculosis-in-myanmar-burden-and-mutations-causing-second-line-drug-resistance
#19
P W Ei, W W Aung, W W Nyunt, T L Swe, M M Htwe, S M Win, S T Aung, C L Chang, H-Y Lee, J S Lee
SETTING: Two tuberculosis (TB) reference laboratories in Myanmar. OBJECTIVES: To determine the proportion of extensively drug-resistant TB (XDR-TB) cases among multidrug-resistant TB (MDR-TB) cases and the mutations that cause resistance to second-line drugs in Myanmar. DESIGN: This was a cross-sectional, retrospective study. Multidrug-resistant Mycobacterium tuberculosis isolates were collected during 2015-2016. Phenotypic drug susceptibility testing (DST) was performed and drug-resistant mutations identified by sequencing...
January 1, 2018: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29274493/1-3-5-triazaspiro-5-5-undeca-2-4-dienes-as-selective-mycobacterium-tuberculosis-dihydrofolate-reductase-inhibitors-with-potent-whole-cell-activity
#20
Xuan Yang, Wassihun Wedajo, Yoshiyuki Yamada, Sue-Li Dahlroth, Jason Jun-Long Neo, Thomas Dick, Wai-Keung Chui
The emergence of multi- and extensively-drug resistant tubercular (MDR- and XDR-TB) strains of mycobacteria has limited the use of existing therapies, therefore new drugs are needed. Dihydrofolate reductase (DHFR) has recently attracted much attention as a target for the development of anti-TB agents. This study aimed to develop selective M. tuberculosis DHFR inhibitors using rationale scaffolding design and synthesis, phenotype-oriented screening, enzymatic inhibitory study, whole cell on-target validation, molecular modeling, and in vitro DMPK determination to derive new anti-TB agents...
December 7, 2017: European Journal of Medicinal Chemistry
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