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https://www.readbyqxmd.com/read/28544982/an-evaluation-of-minor-groove-binders-as-anti-fungal-and-anti-mycobacterial-therapeutics
#1
Fraser J Scott, Ryan J O Nichol, Abedawn I Khalaf, Federica Giordani, Kirsten Gillingwater, Soumya Ramu, Alysha Elliott, Johannes Zuegg, Paula Duffy, Michael-Jon Rosslee, Lerato Hlaka, Santosh Kumar, Mumin Ozturk, Frank Brombacher, Michael Barrett, Reto Guler, Colin J Suckling
This study details the synthesis and biological evaluation of a collection of 19 structurally related Minor Groove Binders (MGBs), derived from the natural product distamycin, which were designed to probe antifungal and antimycobacterial activity. From this initial set, we report several MGBs that are worth more detailed investigation and optimisation. MGB-4, MGB-317 and MGB-325 have promising MIC80s of 2, 4 and 0.25 μg/mL, respectively, against the fungus C. neoformans.MGB-353 and MGB-354 have MIC99s of 3...
May 17, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28539734/honey-and-health-a-review-of-recent-clinical-research
#2
REVIEW
Saeed Samarghandian, Tahereh Farkhondeh, Fariborz Samini
Honey is one of the most appreciated and valued natural products introduced to humankind since ancient times. Honey is used not only as a nutritional product but also in health described in traditional medicine and as an alternative treatment for clinical conditions ranging from wound healing to cancer treatment. The aim of this review is to emphasize the ability of honey and its multitude in medicinal aspects. Traditionally, honey is used in the treatment of eye diseases, bronchial asthma, throat infections, tuberculosis, thirst, hiccups, fatigue, dizziness, hepatitis, constipation, worm infestation, piles, eczema, healing of ulcers, and wounds and used as a nutritious supplement...
April 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/28535545/portuguese-recommendations-for-the-use-of-methotrexate-in-rheumatic-diseases-2016-update
#3
Ana Catarina Duarte, Daniela Santos-Faria, Maria João Gonçalves, Alexandre Sepriano, Ana Filipa Mourão, Cátia Duarte, Joana Sousa Neves, Ana Filipa Águeda, Pedro Ávila Ribeiro, Alexandra Daniel, Adriano Neto, Ana Cordeiro, Ana Rodrigues, Anabela Barcelos, Cândida Silva, Cristina Ponte, Elsa Vieira-Sousa, Filipa Teixeira, Filipa Oliveira-Ramos, Filipe Araújo, Filipe Barcelos, Helena Canhão, Helena Santos, João Ramos, Joaquim Pereira, José Costa, José António Melo Gomes, Luís Cunha-Miranda, Lúcia Costa, Marcos Cerqueira, Margarida Cruz, Maria José Santos, Miguel Bernardes, Paula Oliveira, Pedro Abreu, Ricardo Figueira, Rita Barros, Sandra Falcão, Patrícia Pinto, Sofia Pimenta, Susana Capela, Vitor Teixeira, João Eurico Fonseca
BACKGROUND: Methotrexate (MTX) is the first-line drug in the treatment of rheumatoid arthritis (RA) and the most commonly prescribed disease modifying anti-rheumatic drug. Moreover, it is also used as an adjuvant drug in patients under biologic therapies, enhancing the efficacy of biologic agents. OBJECTIVES: To review the literature and update the Portuguese recommendations for the use of MTX in rheumatic diseases first published in 2009. METHODS: The first Portuguese guidelines for the use of MTX in rheumatic diseases were published in 2009 and were integrated in the multinational 3E Initiative (Evidence Expertise Exchange) project...
May 9, 2017: Acta Reumatológica Portuguesa
https://www.readbyqxmd.com/read/28527127/evaluation-of-heparg-cells-for-the-assessment-of-indirect-drug-induced-hepatotoxicity-using-inh-as-a-model-substance
#4
Anika Mann, Thomas Pelz, Knut Rennert, Alexander Mosig, Michael Decker, Amelie Lupp
HepaRG cells are widely used as an in vitro model to assess drug-induced hepatotoxicity. However, only few studies exist so far regarding their suitability to detect the effects of drugs requiring a preceding activation via the cytochrome P450 (CYP) system. A prototypic substance is the anti-tuberculosis agent INH, which is metabolized into N-acetylhydrazine, which then triggers hepatotoxicity. Therefore, the aim of the present study was to test if this effect can also be detected in HepaRG cells and if it can be counteracted by the known hepatoprotectant silibinin...
May 19, 2017: Human Cell
https://www.readbyqxmd.com/read/28521188/bis-diphenylphosphino-amines-containing-ruthenium-cymene-complexes-as-potential-anti-mycobacterium-tuberculosis-agents
#5
Juliana P da Silva, Isabel C Silva, Fernando R Pavan, Davi F Back, Márcio P de Araujo
Several ruthenium complexes have been investigated regarding anti-Mycobacterium tuberculosis (anti-MTb) activity, with some diphosphine-containing ruthenium complexes comparable to first and second line drugs. However, to the best of our knowledge, there is no PNP-containing ruthenium complexes applied as metallodrugs. Thus, this study focused on the synthesis, characterization and anti-MTb activity of a new series of coordination compounds with general formula [RuCl(η(6)-p-cymene)(PN(R)P)]X (R=CH2Py (Py=pyridine)-[1a], CH2Ph (Ph=phenyl)-[1b], Ph-[1c] and p-tol (p-tol=p-tolyl)-[1d]; X=PF6(-) or BF4(-))...
April 9, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28507894/re-administration-of-abatacept-for-the-control-of-articular-symptoms-of-rheumatoid-arthritis-during-anti-tuberculous-therapy
#6
Hironori Kawamoto, Jin Takasaki, Satoru Ishii, Manabu Suzuki, Eriko Morino, Go Naka, Motoyasu Iikura, Shinyu Izumi, Yuichiro Takeda, Haruhito Sugiyama
This case report describes the re-administration of abatacept to successfully reduce the articularsymptoms of a patient with rheumatoid arthritisduring the intensive phase of anti-tuberculous therapy. A 75-year-old man developed active pulmonary tuberculosis during the administration of abatacept for rheumatoid arthritis. The patient experienced a paradoxical reaction and exacerbation of rheumatoid arthritis that caused us to discontinue the abatacept. Later re-administration of abatacept along with anti-tuberculosis treatment led to well-controlled rheumatoid arthritis without exacerbation of the tuberculosis...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28494250/recent-developments-of-coumarin-containing-derivatives-and-their-anti-tubercular-activity
#7
Yuan-Qiang Hu, Zhi Xu, Shu Zhang, Xiang Wu, Jun-Wei Ding, Zao-Sheng Lv, Lian-Shun Feng
Tuberculosis (TB) is a lift-threatening chronic deadliest infectious disease caused predominantly by Mycobacterium tuberculosis (MTB) which affects primarily the lungs (pulmonary TB) apart from other vital organs. The emergence of drug-resistant TB (DR-TB), multidrug-resistant TB (MDR-TB), extensively drug-resistant TB (XDR-TB) and the recently cases of totally drug resistant (TDR) towards currently accessible standard drugs was increased up to alarming level in the recent decades. In pursuit of searching new anti-TB agents, numerous of derivatives have been synthesized and screened for their anti-TB activity...
May 2, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28490012/is-the-prophylactic-use-of-hepatoprotectants-necessary-in-anti-tuberculosis-treatment
#8
Li Xu, Fei Zhang, Chen Xu, Kai-Ge Liu, Wei Wu, Ying-Xuan Tian
BACKGROUND: Liver injury is one of the serious side effects of anti-tuberculosis (TB) drugs. It is controversial whether hepatoprotectant prophylaxis is efficient and safe in anti-TB treatment, so we aimed to assess the efficacy and safety of hepatoprotectant prophylaxis in patients who had received anti-TB treatment. METHODS: PubMed, the Cochrane library, Embase, Ovid, Springer link, Wiley, Elsevier, Web of Science, and the Karger Online Journal were systematically searched prior to April 2016 for articles related to hepatoprotectant prophylaxis in the treatment of TB...
May 11, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28482292/new-drugs-for-the-treatment-of-mycobacterium-tuberculosis-infection
#9
REVIEW
Manaf AlMatar, Husam AlMandeal, Işıl Var, Begüm Kayar, Fatih Köksal
Tuberculosis presents a grave challenge to health, globally instigating 1.5 million mortalities each year. Following the breakthrough of first-line anti-TB medication, the number of mortalities reduced greatly; nonetheless, the swift appearance of tuberculosis which was drug-resistant, as well as the capability of the bacterium to survive and stay dormant are a considerable problem for public health. In order to address this issue, several novel possible candidates for tuberculosis therapy have been subjected to clinical trials of late...
May 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28469152/lineage-specific-snps-for-genotyping-of-mycobacterium-tuberculosis-clinical-isolates
#10
Horng-Yunn Dou, Chien-Hsing Lin, Yih-Yuan Chen, Shiu-Ju Yang, Jia-Ru Chang, Keh-Ming Wu, Ying-Tsong Chen, Pei-Ju Chin, Yen-Ming Liu, Ih-Jen Su, Shih-Feng Tsai
Tuberculosis (TB) is a severe infectious disease worldwide. Genetic variation of the causative agent, Mycobacterium tuberculosis (MTB), determines the outcomes of infection and anti-TB treatment. Until recently, there has been no effective and convenient way for classifying clinical isolates based on the DNA sequences of the divergent lineages of MTB infecting human populations. Here, we identified single nucleotide polymorphisms (SNPs) of six representative strains from Taiwan by whole-genome sequencing and comparing the results to the sequence of the H37Rv reference strain...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28465652/magnitude-of-antiretroviral-drug-toxicity-in-adult-hiv-patients-in-ethiopia-a-cohort-study-at-seven-teaching-hospitals
#11
Esayas Kebede Gudina, Alula M Teklu, Asres Berhan, Atsbeha Gebreegziabhier, Teshome Seyoum, Abiy Nega, Girmay Medhin, Amha Kebede, Yibeltal Assefa
BACKGROUND: The introduction of antiretroviral therapy (ART) has resulted in significant mortality reduction and improvement in the quality of life. However, this has come at a cost of increased drug toxicity. The objective of this study was to assess the patterns and predictors of ART toxicity in adult HIV patients in Ethiopia. METHODS: This is a prospective cohort study conducted at seven teaching hospitals between September 2009 and December 2013 involving 3921 HIV patients on ART...
February 2017: Ethiopian Journal of Health Sciences
https://www.readbyqxmd.com/read/28465626/synthesis-and-biological-evaluation-of-indole-core-based-derivatives-with-potent-antibacterial-activity-against-resistant-bacterial-pathogens
#12
Wei Hong, Jingyang Li, Zhe Chang, Xiaoli Tan, Hao Yang, Yifan Ouyang, Yanhui Yang, Sargit Kaur, Ian C Paterson, Yun Fong Ngeow, Hao Wang
The emergence of drug resistance in bacterial pathogens is a growing clinical problem that poses difficult challenges in patient management. To exacerbate this problem, there is currently a serious lack of antibacterial agents that are designed to target extremely drug-resistant bacterial strains. Here we describe the design, synthesis and antibacterial testing of a series of 40 novel indole core derivatives, which are predicated by molecular modeling to be potential glycosyltransferase inhibitors. Twenty of these derivatives were found to show in vitro inhibition of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus...
May 3, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28462696/hybrid-docking-qsar-studies-of-1-4-dihydropyridine-3-5-dicarboxamides-as-potential-antitubercular-agents
#13
Yasaman Rasouli, Asghar Davood
BACKGROUND: Tuberculosis is one of the main medical problems that some people are suffering still from this infectious disease. 1, 4-dihydropyridines are a multi-target ligands that recently are recognized as an anti-tubercular agents. METHOD: In the current research we did computational studies of some synthesized 1, 4-dihydropyridine-3, 5-dicarboxamides in non-hydrolyzed and hydrolyzed forms to find the drug-receptor interactions profile. RESULTS: Among equations that obtained for non-hydrolyzed compounds, the model with better statistical parameters such as R2= 0...
April 26, 2017: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/28458316/fatal-unusual-miliary-tuberculosis-in-which-a-patient-developed-acute-respiratory-distress-syndrome-induced-by-infliximab-an-autopsy-case-report
#14
Shion Miyoshi, Jin Takasaki, Sohtaro Mine, Masanori Kono, Toru Igari, Yuichiro Takeda, Masayuki Hojo, Haruhito Sugiyama
Anti-tumor necrosis factor α (anti-TNFα) agents increase the risk of tuberculosis (TB), but cases are rarely fatal. This report concerns a patient who was undergoing treatment with infliximab and presented with acute respiratory distress syndrome due to miliary TB without a miliary shadow. The findings of a pathological autopsy revealed innumerable granulomas in the organs, and the miliary nodules in the lung consisted of more unstructured granulomas. Anti-TNFα agents are unusual in the presentation of TB...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28458043/targeting-isocitrate-lyase-for-the-treatment-of-latent-tuberculosis
#15
REVIEW
Ram Prasad Bhusal, Ghader Bashiri, Brooke X C Kwai, Jonathan Sperry, Ivanhoe K H Leung
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that can remain dormant for many years before becoming active. One way to control and eliminate TB is the identification and treatment of latent TB, preventing infected individuals from developing active TB and thus eliminating the subsequent spread of the disease. Isocitrate lyase (ICL) is involved in the mycobacterial glyoxylate and methylisocitrate cycles. ICL is important for the growth and survival of M. tuberculosis. ICL is not present in humans and is therefore a potential therapeutic target for the development of anti-TB agents...
April 27, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28456911/qsar-based-therapeutic-management-of-m-tuberculosis
#16
REVIEW
Shahzaib Ahamad, Safikur Rahman, Faez Iqbal Khan, Neeraja Dwivedi, Sher Ali, Jihoe Kim, Md Imtaiyaz Hassan
Mycobacterium tuberculosis is responsible for severe mortality and morbidity worldwide but, under-developed and developing countries are more prone to infection. In search of effective and wide-spectrum anti-tubercular agents, interdisciplinary approaches are being explored. Of the several approaches used, computer based quantitative structure activity relationship (QSAR) have gained momentum. Structure-based drug design and discovery implies a combined knowledge of accurate prediction of ligand poses with the good prediction and interpretation of statistically validated models derived from the 3D-QSAR approach...
April 29, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28451321/expedient-synthesis-of-the-heneicosasaccharyl-mannose-capped-arabinomannan-of-the-mycobacterium-tuberculosis-cellular-envelope-by-glycosyl-carbonate-donors
#17
Maidul Islam, Ganesh P Shinde, Srinivas Hotha
The global incidence of tuberculosis is increasing at an alarming rate, and Mycobacterium tuberculosis (Mtb) is the causative agent for tuberculosis, a disease with high mortality. Lipoarabinomannan (LAM) is one of the major components of the Mtb cellular envelope and is an attractive scaffold for developing anti-tubercular drugs, vaccines and diagnostics. Herein, a highly convergent strategy is developed to synthesize heneicosasaccharyl arabinomannan for the first time. The arabinomannan synthesized in this endeavour has several 1,2-trans or α-Araf linkages and three 1,2-cis or β-Araf linkages end capped with 1,2-trans or α-Manp linkages...
March 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28451184/combatting-amr-photoactivatable-ruthenium-ii-isoniazid-complex-exhibits-rapid-selective-antimycobacterial-activity
#18
Nichola A Smith, Pingyu Zhang, Simon E Greenough, Michael D Horbury, Guy J Clarkson, Daniel McFeely, Abraha Habtemariam, Luca Salassa, Vasilios G Stavros, Christopher G Dowson, Peter J Sadler
The novel photoactive ruthenium(ii) complex cis-[Ru(bpy)2(INH)2][PF6]2 (1·2PF6, INH = isoniazid) was designed to incorporate the anti-tuberculosis drug, isoniazid, that could be released from the Ru(ii) cage by photoactivation with visible light. In aqueous solution, 1 rapidly released two equivalents of isoniazid and formed the photoproduct cis-[Ru(bpy)2(H2O)2](2+) upon irradiation with 465 nm blue light. We screened for activity against bacteria containing the three major classes of cell envelope: Gram-positive Bacillus subtilis, Gram-negative Escherichia coli, and Mycobacterium smegmatis in vitro using blue and multi-colored LED multi-well arrays...
January 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28446822/anti-mycobacterium-activity-of-microbial-peptides-in-a-silkworm-infection-model-with-mycobacterium-smegmatis
#19
Akiho Yagi, Ryuji Uchida, Hiroshi Hamamoto, Kazuhisa Sekimizu, Ken-Ichi Kimura, Hiroshi Tomoda
An in vivo-mimic silkworm infection model with Mycobacterium smegmatis was established. When silkworms were raised at 37 °C following an injection of M. smegmatis cells (1.25 × 10(7) CFU larva(-1) g(-1)) into the silkworm hemolymph, they died within 48 h. Under these conditions, four microbial peptides with anti-M. smegmatis activity, lariatin A, calpinactam, lysocin E and propeptin, exerted therapeutic effects in a dose-dependent manner, and these are also clinically used agents that are active against Mycobacterium tuberculosis...
May 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28428773/mutation-at-g103-of-mtbftsz-altered-their-sensitivity-to-coumarins
#20
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
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