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https://www.readbyqxmd.com/read/28994619/biological-evaluation-of-benzosuberones
#1
Haider Behbehani, Kamal M Dawood, Thoraya A Farghaly
Several natural products containing benzosuberone moiety are clinically reported as anti-tumor agents. Furthermore, several synthetic benzosuberones cited in this review exhibited wide range of theraputic activities such as bacteriostatic, anti-inflammatory, antidepressants and anti-tumor activities. Our recent review provides an overview of the different methods to synthesize the benzosuberones and their extensive biological activities. Areas covered: Thirty-two patents among 130 references are cited in this review that covered the recent inhibitory activities of the benzosuberone scaffolds and their broad area of biological applications up to the first quarter of 2017...
October 10, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28986117/screening-prophylaxis-and-counselling-before-the-start-of-biological-therapies-a-practical-approach-focused-on-ibd-patients
#2
REVIEW
Cândida Abreu, António Sarmento, Fernando Magro
The standard of care in the management of immune-mediated inflammatory conditions relies on immunomodulators, glucocorticoids, and biologicals (including anti-tumour necrosis factor -α and other monoclonal antibodies). These agents have an overall favourable benefit/risk ratio; however, they modulate the immune response as part of their mechanisms of action, and therefore they may increase the risk of developing infections, particularly in older patients or in patients with concomitant corticosteroids. Some of these infections may be preventable by immunization, chemoprophylaxis or counselling...
September 12, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28982200/a-baculovirus-conjugated-mimotope-vaccine-targeting-mycobacterium-tuberculosis-lipoarabinomannan
#3
Hyun-Jin Shin, Luis H Franco, Vidhya R Nair, Angela C Collins, Michael U Shiloh
Mycobacterium tuberculosis, the causative agent of tuberculosis, is a major cause of morbidity and mortality worldwide. However, an effective vaccine for M. tuberculosis is lacking. We panned a phage display library using monoclonal antibodies against M. tuberculosis liporabinomannan (LAM), an important component of the M. tuberculosis cell wall, and identified two peptide sequences, HSFKWLDSPRLR or SGVYKVAYDWQH, with high antibody affinity after multiple rounds of panning. Only the HSFKWLDSPRLR peptide induced an anti-LAM response when conjugated to either keyhole limpet hemocyanin (KLH) or to the baculovirus Autographa californica multicapsid nucleopolyherovirus (AcMNPV) when introduced into mice by injection or via intranasal inoculation, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28972145/structural-analyses-of-the-mazef4-toxin-antitoxin-pair-in-mycobacterium-tuberculosis-provide-evidence-for-a-unique-extracellular-death-factor
#4
Do-Hwan Ahn, Ki-Young Lee, Sang Jae Lee, Sung Jean Park, Hye-Jin Yoon, Soon-Jong Kim, Bong-Jin Lee
The bacterial toxin-antitoxin MazEF system in the tuberculosis (TB)-causing bacterium Mycobacterium tuberculosis is activated under unfavorable conditions, including starvation, antibiotic exposure, and oxidative stress. This system contains the ribonucleolytic enzyme MazF and has emerged as a promising drug target for TB treatments targeting the latent stage of M. tuberculosis infection and reportedly mediates a cell death process via a peptide called extracellular death factor (EDF). Although it is well established that the increase in EDFmediated toxicity of MazF drives a cell-killing phenomenon, the molecular details are poorly understood...
October 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28961913/evaluation-of-minor-groove-binders-mgbs-as-novel-anti-mycobacterial-agents-and-the-effect-of-using-non-ionic-surfactant-vesicles-as-a-delivery-system-to-improve-their-efficacy
#5
Lerato Hlaka, Michael-Jon Rosslee, Mumin Ozturk, Santosh Kumar, Suraj P Parihar, Frank Brombacher, Abedawn I Khalaf, Katharine C Carter, Fraser J Scott, Colin J Suckling, Reto Guler
Objectives: The slow development of major advances in drug discovery for the treatment of Mycobacterium tuberculosis ( Mtb ) infection suggests a compelling need for evaluation of more effective drug therapies against TB. New classes of drugs are constantly being evaluated for anti-mycobacterial activity with currently a very limited number of new drugs approved for TB treatment. Minor groove binders (MGBs) have previously revealed promising antimicrobial activity against various infectious agents; however, they have not yet been screened against Mtb ...
September 18, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28944155/choroidal-neovascular-membrane-in-intraocular-tuberculosis
#6
Koushik Tripathy
Recently, Lodhi SA and colleagues have reported on a patient with choroidal neovascular membrane (CNVM) associated with tubercular granuloma, who responded to intravitreal bevacizumab injections. The available literature regarding CNVM associated with intraocular tuberculosis is briefly discussed. Choroidal neovascular membrane is a possible complication of choroidal tuberculosis and the patients should be informed about this risk. However, patients usually respond well to intravitreal anti-vascular endothelial growth factor agents as evidenced by the case reported by us and the current case reported by Lodhi et al...
2017: GMS Ophthalmology Cases
https://www.readbyqxmd.com/read/28941848/drug-development-against-tuberculosis-past-present-and-future
#7
REVIEW
Mahesh S Vasava, Manoj N Bhoi, Sanjay K Rathwa, Mayuri A Borad, Sneha G Nair, Hitesh D Patel
Infection of Mycobacterium tuberculosis (MTB) was observed as early as 5000 years ago with evidence, which is a primeval enemy of the humanoid race. MTB is the pathogen which is responsible for causing the infectious disease tuberculosis; it remains a major cause of morbidity and mortality in poor low-income countries as well as in developing countries because of non-availability of reliable laboratory facilities. The current treatment for drug-resistant tuberculosis (TB) is lengthy, complex, and connected with severe harmful side effects and poor outcomes...
October 2017: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/28936965/-important-role-of-interleukin-35-in-infectious-diseases-and-its-significance
#8
Renqi Yao, Yao Wu, Bing Ma
Infectious diseases are resulted from the invasion of an organism's body tissues by multiple disease-causing agents. It has been demonstrated that the occurrence and development of infectious diseases are closely associated with the functional status of immune system. Cytokines play significant roles in modulating the host immune response to the clearance of pathogenic microorganisms and maintaining immune homeostasis. Interleukin-35 (IL-35), as a newly identified member of IL-12 family, exerts suppressive effect on immune response by means of a specific pattern...
September 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28932591/a-case-of-tuberculosis-reactivation-suspected-of-cancer-progression-during-oral-tyrosine-kinase-inhibitor-treatment-in-a-patient-diagnosed-as-non-small-cell-lung-cancer
#9
Hwa Young Lee, Jin Woo Kim, Chang Dong Yeo
We report a first case of a patient experiencing reactivation of pulmonary tuberculosis (TB) during treatment of oral tyrosine kinase inhibitor (TKI) with non-small cell lung cancer (NSCLC). A 44-year-old male patient visited the hospital with cough. He had been treated with erlotinib (oral TKI) for 8 months after being diagnosed as NSCLC with sensitive epidermal growth factor receptor mutation in our clinic. At initial chest imaging, the patient had fibroatelectatic calcified granuloma in the right upper lobe (RUL) apex as well as 1...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28927812/bi-pssm-position-specific-scoring-matrix-based-intelligent-computational-model-for-identification-of-mycobacterial-membrane-proteins
#10
Muslim Khan, Maqsood Hayat, Sher Afzal Khan, Saeed Ahmad, Nadeem Iqbal
Mycobacterium is a pathogenic bacterium, which is a causative agent of tuberculosis (TB) and leprosy. These diseases are very crucial and become the cause of death of millions of people every year in the world. So, the characterize structure of membrane proteins of the protozoan play a vital role in the field of drug discovery because, without any knowledge about this Mycobacterium's membrane protein and their types, the scientists are unable to treat this pathogenic protozoan. So, an accurate and competitive computational model is needed to characterize this uncharacterized structure of mycobacterium...
December 21, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28895050/design-of-2-nitroimidazooxazine-derivatives-as-deazaflavin-dependent-nitroreductase-ddn-activators-as-anti-mycobacterial-agents-based-on-3d-qsar-hqsar-and-docking-study-with-in-silico-prediction-of-activity-and-toxicity
#11
Nirzari Gupta, Vivek K Vyas, Bhumika D Patel, Manjunath Ghate
Deazaflavin-dependent nitroreductase (Ddn) is an emerging target in the field of anti-tuberculosis agents. In the present study, 2-nitroimidazooxazine derivatives as Ddn activators were aligned for CoMFA, CoMSIA and HQSAR analysis. The best CoMFA and CoMSIA model were generated with leave-one-out correlation coefficients (q (2)) of 0.585 and 0.571, respectively. Both the CoMFA and CoMSIA models were also validated by a test set of 11 compounds with satisfactory [Formula: see text] value of 0.701 and 0.667, respectively...
September 11, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/28892927/a-rare-instance-of-levofloxacin-induced-myoclonus
#12
Sushil Kiran Kunder, A Avinash, Veena Nayak, Amod Tilak
Levofloxacin is a widely used fluoroquinolone, mainly as a respiratory antimicrobial agent. It is employed as a second line therapeutic modality in pulmonary tuberculosis as well. The drug has been in use for ages, and is known to be both efficacious and safe. However, it is not free of adverse effects. The most dangerous ones are those involving the Central Nervous System (CNS). Although rare, levofloxacin can cause involuntary movements like chorea and myoclonus. Here by, we present a case of an elderly male patient who developed reversible myoclonus/chorea after a course of levofloxacin (which was initiated as part of his anti-tubercular therapy) following the development of peripheral neuropathy secondary to isoniazid...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28892605/inhibitors-of-the-diadenosine-tetraphosphate-phosphorylase-rv2613c-of-mycobacterium-tuberculosis
#13
Kathrin H Götz, Stephan M Hacker, Daniel Mayer, Jan-Niklas Dürig, Steffen Stenger, Andreas Marx
The intracellular concentration of diadenosine tetraphospate (Ap4A) increases upon exposure to stress conditions. Despite being discovered over 50 years ago, the cellular functions of Ap4A are still enigmatic. If and how the varied Ap4A is a signal and involved in the signaling pathways leading to an appropriate cellular response remain to be discovered. Because the turnover of Ap4A by Ap4A cleaving enzymes is rapid, small molecule inhibitors for these enzymes would provide tools for the more detailed study of the role of Ap4A...
September 26, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28870161/chronic-dialysis-nat2-polymorphisms-and-the-risk-of-isoniazid-induced-encephalopathy-case-report-and-literature-review
#14
Stefan Matei Constantinescu, Benoit Buysschaert, Vincent Haufroid, Franck Broly, Michel Jadoul, Johann Morelle
BACKGROUND: Isoniazid is the most widely used anti-tuberculosis agent, yet it may lead to life-threatening complications. CASE PRESENTATION: Here we report the case of a chronic hemodialysis patient who developed severe encephalopathy after the start of isoniazid. Blood levels of isoniazid were elevated, and acetyl-isoniazid over isoniazid ratio was decreased 3 h after intake of the medication, suggesting that a slow acetylator phenotype may have contributed to drug toxicity, in addition to pyridoxal phosphate removal by dialysis...
September 4, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28869400/azide-alkyne-cycloaddition-en-route-to-4-aminoquinoline-ferrocenylchalcone-conjugates-synthesis-and-anti-tb-evaluation
#15
Amandeep Singh, Albertus Viljoen, Laurent Kremer, Vipan Kumar
AIM: Tuberculosis is responsible for 9.6 million infections and 1.5 million deaths in 2015. The development of multidrug-resistant and extensively drug-resistant strains has impeded the development of effective antitubercular therapy. Results/methodology: The present manuscript describes the synthesis of a series of 4-aminoquinoline-ferrocenylchalcone conjugates via Cu-promoted Huisgen's azide-alkyne cycloaddition reaction and evaluation of their antitubercular activities against mc(2)6230 strain of Mycobacterium tuberculosis...
September 4, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28855504/biosynthesis-of-ilamycins-featuring-unusual-building-blocks-and-engineered-production-of-enhanced-anti-tuberculosis-agents
#16
Junying Ma, Hongbo Huang, Yunchang Xie, Zhiyong Liu, Jin Zhao, Chunyan Zhang, Yanxi Jia, Yun Zhang, Hua Zhang, Tianyu Zhang, Jianhua Ju
Tuberculosis remains one of the world's deadliest communicable diseases, novel anti-tuberculosis agents are urgently needed due to severe drug resistance and the co-epidemic of tuberculosis/human immunodeficiency virus. Here, we show the isolation of six anti-mycobacterial ilamycin congeners (1-6) bearing rare L-3-nitro-tyrosine and L-2-amino-4-hexenoic acid structural units from the deep sea-derived Streptomyces atratus SCSIO ZH16. The biosynthesis of the rare L-3-nitrotyrosine and L-2-amino-4-hexenoic acid units as well as three pre-tailoring and two post-tailoring steps are probed in the ilamycin biosynthetic machinery through a series of gene inactivation, precursor chemical complementation, isotope-labeled precursor feeding experiments, as well as structural elucidation of three intermediates (6-8) from the respective mutants...
August 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28842600/inhibiting-mycobacterial-tryptophan-synthase-by-targeting-the-inter-subunit-interface
#17
Katherine A Abrahams, Jonathan A G Cox, Klaus Fütterer, Joaquín Rullas, Fátima Ortega-Muro, Nicholas J Loman, Patrick J Moynihan, Esther Pérez-Herrán, Elena Jiménez, Jorge Esquivias, David Barros, Lluís Ballell, Carlos Alemparte, Gurdyal S Besra
Drug discovery efforts against the pathogen Mycobacterium tuberculosis (Mtb) have been advanced through phenotypic screens of extensive compound libraries. Such a screen revealed sulfolane 1 and indoline-5-sulfonamides 2 and 3 as potent inhibitors of mycobacterial growth. Optimization in the sulfolane series led to compound 4, which has proven activity in an in vivo murine model of Mtb infection. Here we identify the target and mode of inhibition of these compounds based on whole genome sequencing of spontaneous resistant mutants, which identified mutations locating to the essential α- and β-subunits of tryptophan synthase...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28826595/corrigenda-to-elaboration-of-a-proprietary-thymidylate-kinase-inhibitor-motif-towards-anti-tuberculosis-agents-bioorg-med-chem-24-2016-5172-5182
#18
Lijun Song, Martijn D P Risseeuw, Matheus Froeyen, Izet Karalic, Jan Goeman, Davie Cappoen, Johan Van der Eycken, Paul Cos, Hélène Munier-Lehmann, Serge Van Calenbergh
No abstract text is available yet for this article.
August 18, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28818767/recent-advances-of-pyrazole-containing-derivatives-as-anti-tubercular-agents
#19
REVIEW
Zhi Xu, Chuan Gao, Qing-Cheng Ren, Xu-Feng Song, Lian-Shun Feng, Zao-Sheng Lv
One-third of the world's population infected tuberculosis (TB), and more than 1 million deaths annually. The co-infection between the mainly pathogen Mycobacterium tuberculosis (MTB) and HIV, and the incidence of drug-resistant TB, multi-drug resistant TB, extensively drug-resistant TB as well as totally drug-resistant TB have further aggravated the mortality and spread of this disease. Thus, there is an urgent need to develop novel anti-TB agents against both drug-susceptible and drug-resistant TB. The wide spectrum of biological activities and successful utilization of pyrazole-containing drugs in clinic have inspired more and more attention towards this kind of heterocycles...
October 20, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28808382/allium-sativum-constituents-exhibit-anti-tubercular-activity-in-vitro-and-in-raw-264-7-mouse-macrophage-cells-infected-with-mycobacterium-tuberculosis-h37rv
#20
Swapna S Nair, Sujay S Gaikwad, Savita P Kulkarni, Alka Pravin Mukne
BACKGROUND: Long duration of treatment, side-effects of currently used anti-tubercular drugs and emergence of drug-resistant forms of Mycobacterium tuberculosis (MTB) warrants the need to develop new drugs to tackle the scourge of tuberculosis (TB). Garlic is an edible plant reported to have anti-tubercular activity. However, previous researches on anti-tubercular effect of garlic were focused mostly on preliminary in vitro screening. OBJECTIVE: To identify constituents responsible for anti-tubercular activity of thiosulfinate-derivative rich extract of garlic (GE) and to evaluate activity of the most active constituent in RAW 264...
July 2017: Pharmacognosy Magazine
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