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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/28544837/candida-endocarditis-a-review-of-twelve-episodes-in-eleven-patients
#2
Tatjana Lejko Zupanc, Mateja Logar
BACKGROUND: Candida spp. are a rare but important cause of infective endocarditis. The study aim was to describe pertinent clinical data on consecutive patients with Candida endocarditis treated at a tertiary referral center between 1984 and 2013. METHODS: A retrospective search of the authors' endocarditis database was performed and the medical records of patients with confirmed Candida endocarditis were reviewed. Important data relating to demographics, medical history and clinical data, as well as information on outcome and treatment, were extracted...
January 2017: Journal of Heart Valve Disease
https://www.readbyqxmd.com/read/28544681/tenebrio-molitor-gram-negative-binding-protein-3-tmgnbp3-is-essential-for-inducing-downstream-antifungal-tenecin-1-gene-expression-against-infection-with-beauveria-bassiana-jef-007
#3
Yi-Ting Yang, Mi Rong Lee, Se Jin Lee, Sihyeon Kim, Yu-Shin Nai, Jae Su Kim
The Toll signaling pathway is responsible for defense against both Gram-positive bacteria and fungi. Gram-negative binding protein 3 (GNBP3) has a strong affinity for the fungal cell wall component, β-1,3-glucan, which can activate the prophenoloxidase (proPO) cascade and induce the Toll signaling pathway. Myeloid differentiation factor 88 (MyD88) is an intracellular adaptor protein involved in the Toll signaling pathway. In this study, we monitored the response of 5 key genes (TmGNBP3, TmMyD88, and Tenecin 1, 2, and 3) in the Toll pathway of the mealworm Tenebrio molitor immune system against the fungus Beauveria bassiana JEF-007 using RT-PCR...
May 23, 2017: Insect Science
https://www.readbyqxmd.com/read/28543298/synthesis-and-preclinical-pharmacokinetic-study-of-dha-10-a-novel-potential-antifungal-pogostone-analogue
#4
Ming Liu, Yanfen Zhou, Jianwei Zhu, Bo Ma, Zheng Fang, Qi Zhang
OBJECTIVES: The emergence of fungal disease calls for the urgency of development of novel drug. In this study, we developed a novel pogostone analogue, DHA-10 and investigated its preclinical pharmacokinetics, tissue distribution, excretion and protein binding rate in rats. METHODS: DHA-10 was synthesized with dehydroacetic acid (DHA) as the starting material and the structure confirmed by NMR and HRMS. The LC-MS/MS was applied to quantitative analysis of DHA-10 concentrations in the biological samples...
May 23, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28542595/antifungal-tc17-cells-are-durable-and-stable-persisting-as-long-lasting-vaccine-memory-without-plasticity-towards-ifn%C3%AE-cells
#5
Som Gowda Nanjappa, Andrew J McDermott, J Scott Fites, Kevin Galles, Marcel Wüthrich, George S Deepe, Bruce S Klein
Our understanding of persistence and plasticity of IL-17A+ memory T cells is clouded by conflicting results in models analyzing T helper 17 cells. We studied memory IL-17A+ CD8+ T-cell (Tc17) homeostasis, persistence and plasticity during fungal vaccine immunity. We report that vaccine-induced memory Tc17 cells persist with high fidelity to the type 17 phenotype. Tc17 cells persisted durably for a year as functional IL-17A+ memory cells without converting to IFNγ+ (Tc1) cells, although they produced multiple type I cytokines in the absence of residual vaccine antigen...
May 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28541964/role-of-early-vitrectomy-in-the-treatment-of-fungal-endophthalmitis
#6
Umesh Chandra Behera, Monica Budhwani, Taraprasad Das, Soumyava Basu, Tapas Ranjan Padhi, Manas Ranjan Barik, Savitri Sharma
PURPOSE: To study whether immediate pars plana vitrectomy at the time of sampling vitreous for culture alter the visual and structural outcomes in fungal endophthalmitis. METHODS: Surgical results of 66 consecutive patients with culture-positive fungal endophthalmitis attending a tertiary eye care hospital in eastern India were analyzed. Based on the timing of vitrectomy, they were divided into 2 groups: Group 1-immediate vitrectomy (n = 31) and Group 2-diagnostic vitrectomy alone (n = 35) as the first-line intervention...
May 23, 2017: Retina
https://www.readbyqxmd.com/read/28540871/clinico-mycological-study-of-dermatophytic-infections-and-their-sensitivity-to-antifungal-drugs-in-a-tertiary-care-center
#7
Soniya Mahajan, Ragini Tilak, Satyendra K Kaushal, Rabindra N Mishra, Shyam S Pandey
BACKGROUND: Worldwide, dermatophytic infections are running a chronic course either due to ineffective treatment or emerging drug resistance. In the past three decades, there has been an increase in incidence and non-responsiveness to conventional antifungals, which suggests that there is a need of antifungal sensitivity testing. AIMS: This study was aimed at identifying clinico-mycological pattern of dermatophytic infections in patients attending thedermatology outpatient department of a tertiary care hospital, and to obtain the sensitivity pattern of isolates against six commonly used oral antifungals (fluconazole, terbinafine, itraconazole, ketoconazole, griseofulvin and voriconazole)...
May 22, 2017: Indian Journal of Dermatology, Venereology and Leprology
https://www.readbyqxmd.com/read/28540147/candida-prosthetic-joint-infection-a-review-of-treatment-methods
#8
REVIEW
Fernando Cobo, Javier Rodríguez-Granger, Antonio Sampedro, Luis Aliaga-Martínez, José María Navarro-Marí
Fungal microorganisms are still a rare cause of bone and joint infections. We report a new case of knee prosthetic joint infection due to Candida albicans in a patient with a previous two-stage right knee arthroplasty for septic arthritis due to S. epidermidis occurred several months ago. Moreover, the treatment in 76 cases of Candida prosthetic joint infection has been discussed. Forty patients were female and mean age at diagnosis was 65.7 (± SD 18) yrs. No risk factors for candidal infection were found in 25 patients...
2017: J Bone Jt Infect
https://www.readbyqxmd.com/read/28539938/effects-of-medicinal-plant-extracts-and-photosensitization-on-aflatoxin-producing-aspergillus-flavus-raper-and-fennell
#9
Loise M Njoki, Sheila A Okoth, Peter M Wachira
This study was undertaken with an aim of exploring the effectiveness of medicinal plant extracts in the control of aflatoxin production. Antifungal properties, photosensitization, and phytochemical composition of aqueous and organic extracts of fruits from Solanum aculeastrum, bark from Syzygium cordatum, and leaves from Prunus africana, Ocimum lamiifolium, Lippia kituiensis, and Spinacia oleracea were tested. Spores from four-day-old cultures of previously identified toxigenic fungi, UONV017 and UONV003, were used...
2017: International Journal of Microbiology
https://www.readbyqxmd.com/read/28539243/synthesis-sar-and-molecular-docking-studies-of-benzo-d-thiazole-hydrazones-as-potential-antibacterial-and-antifungal-agents
#10
Gao-Feng Zha, Jing Leng, N Darshini, T Shubhavathi, H K Vivek, Abdullah M Asiri, Hadi M Marwani, K P Rakesh, N Mallesha, Hua-Li Qin
A series of new benzo[d]thiazole-hydrazones analogues were synthesized and screened for their in vitro antibacterial and antifungal activities. The results revealed that compounds 13, 14, 15, 19, 20, 28 and 30 exhibited superior antibacterial potency compared to the reference drug chloramphenicol and rifampicin. Compounds 5, 9, 10, 11, 12, 28 and 30 were found to be good antifungal activity compared to the standard drug ketoconazole. A preliminary study of the structure-activity relationship (SAR) revealed that the antimicrobial activity depended on the effect of different substituents on the phenyl ring...
May 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28538702/translational-development-and-application-of-1%C3%A2-3-%C3%AE-d-glucan-for-diagnosis-and-therapeutic-monitoring-of-invasive-mycoses
#11
REVIEW
Matthew W McCarthy, Ruta Petraitiene, Thomas J Walsh
Early diagnosis and prompt initiation of appropriate antimicrobial therapy are crucial steps in the management of patients with invasive fungal infections. However, the diagnosis of invasive mycoses remains a major challenge in clinical practice, because presenting symptoms may be subtle and non-invasive diagnostic assays often lack sensitivity and specificity. Diagnosis is often expressed on a scale of probability (proven, probable and possible) based on a constellation of imaging findings, microbiological tools and histopathology, as there is no stand-alone assay for diagnosis...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28537063/-consensus-opinion-on-antifungal-prophylaxis-in-haematologic-patients-results-of-the-promic-project
#12
L Vázquez López, T Villaescusa de la Rosa, R de la Cámara, I Espigado, S Grau Cerrato, M Jurado, M Rovira, M Salavert, D Serrano Simonneau, C Solano Vercet, I Ruiz Camps
OBJECTIVE: Invasive fungal disease (IFD) is an important cause of morbidity and mortality in haematological patients. Antifungal prophylaxis (AFP) is indicated for a number of clinical scenarios in this group of patients. The aim of this study was to reach a consensus on IFD prophylaxis in haematological patients in order to optimize their management. METHODS: A committee of experts in haematology and infectious diseases compiled a survey of 79 items with controversial aspects about antifungal prophylaxis in haematological patients...
May 23, 2017: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/28536555/novel-antifungal-activity-for-the-lectin-scytovirin-inhibition-of-cryptococcus-neoformans-and-cryptococcus-gattii
#13
Tyler H Jones, Erin E McClelland, Hana McFeeters, Robert L McFeeters
Pathogenic cryptococci are encapsulated yeast that can cause severe meningoencephalitis. Existing therapeutic options are dated and there is a growing need for new alternative antifungal agents for these fungi. Here we report novel inhibition of pathogenic cryptococci by the antimicrobial lectin Scytovirin. Inhibition was most potent against Cryptococcus neoformans var neoformans and C. gattii, with MFC values of 500 nM. Scytovirin binding was localized to the cell wall and shown to affect capsule size and release...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28536123/randomized-controlled-trial-of-mineralocorticoid-receptor-blockade-in-children-with-chronic-kidney-allograft-nephropathy
#14
Mara Medeiros, Luis Velásquez-Jones, Ana M Hernández, Guillermo Ramón-García, Saúl Valverde, Yolanda Fuentes, Arindal Vargas, Mauricio Patiño, Rosalba Pérez-Villalva, Juan Antonio Ortega-Trejo, Jonatan Barrera-Chimal, Norma A Bobadilla
BACKGROUND AND OBJECTIVES: We showed that mineralocorticoid receptor blockade (MRB) prevented acute and chronic cyclosporine nephropathy (CsA-Nx) in the rat. The aim of this translational study was to investigate the effect of long-term eplerenone administration on renal allograft function in children with biopsy-proven chronic allograft nephropathy (CAN). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Renal transplant children <18 years, biopsy-proven CAN, and a GFR>40 ml/min per 1...
May 23, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28535608/antifungal-activities-of-dimeric-sesquiterpenes-shizukaols-c-and-f-isolated-from-chloranthus-japonicus-sieb
#15
Tae Hoon Kang, Yun Mi Lee, Won Jung Lee, Eui Il Hwang, Ki Duk Park, Gyang Ja Choi, Jae Sun Moon, Ho-Yong Park, Sung Uk Kim
Two dimeric sesquitepenes were separated from Chloranthus japonicus Sieb. and identified as shizukaols C and F. They exhibited potent antifungal activities (MICs = 4-16 μg/ml) in vitro against various plant pathogenic fungi Pythium ultimum, Phytophthora infestans, Botrytis cinerea, Colletotrichum lagenarium, Alternaria kikuchana, and Magnaporthe grisea. Shizukaol C showed 88% and 91% protective activities in the greenhouse against Puccinia recondite (wheat leaf rust) and Phytophthora infestans (tomato late blight), respectively, at 100 µg/ml; shizukaol F exhibited 93% antifungal activity against Puccinia recondite at the same concentration...
May 24, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28535420/evolutionary-changes-in-defensive-specialized-metabolism-in-the-genus-hordeum
#16
Naoki Ube, Miho Nishizaka, Tsuyoshi Ichiyanagi, Kotomi Ueno, Shin Taketa, Atsushi Ishihara
Plants have developed defensive specialized metabolites over the course of evolution. In the genus Hordeum, which includes the important cereal crop barley, specialized metabolites such as hordatines, benzoxazinones, and gramine have been identified. Hordeum species are classified into four clades, H, Xu, Xa, and I. The presence or absence of defensive specialized metabolites was analyzed in representative Hordeum species that included all of the four clades. In the H clade, Hordeum vulgare accumulated hordatines but not benzoxazinones, whereas H...
May 20, 2017: Phytochemistry
https://www.readbyqxmd.com/read/28534905/antimicrobial-peptide-inspired-nh125-analogues-bacterial-and-fungal-biofilm-eradicating-agents-and-rapid-killers-of-mrsa-persisters
#17
Akash Basak, Yasmeen Abouelhassan, Ran Zuo, Hussain Yousaf, Yousong Ding, Robert W Huigens
During microbial infection, antimicrobial peptides are utilized by the immune response to rapidly eradicate microbial pathogens through the destruction of cellular membranes. Inspired by antimicrobial peptides, quaternary ammonium cationic (QAC) compounds have emerged as agents capable of destroying bacterial membranes leading to rapid bacterial death, including the eradication of persistent, surface-attached bacterial biofilms. NH125, an imidazolium cation with a sixteen membered fatty tail, was recently reported to eradicate persister cells and was our starting point for the development of novel antimicrobial agents...
May 23, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28534445/differential-expression-of-micro-rnas-and-their-predicted-targets-in-renal-cells-exposed-to-amphotericin-b-and-its-complex-with-copper-ii-ions
#18
Joanna Magdalena Gola, Barbara Strzałka-Mrozik, Celina Kruszniewska-Rajs, Jolanta Adamska, Mariusz Gagoś, Urszula Mazurek
MicroRNAs (miRNAs) have been reported to regulate essential biological processes, and their expression was shown to be affected by pathological processes and drug-induced toxicity. Amphotericin B (AmB) can cause liver and kidney injury, but a recently developed complex of AmB with copper (II) ions (AmB-Cu(2+)) exhibits a lower toxicity to human renal cells while retaining a high antifungal activity. The aim of our study was to assess AmB-Cu(2+)- induced changes in the miRNA profile of renal cells and to examine which biological processes are significantly affected by AmB-Cu(2+)...
May 23, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28534424/the-bioassay-guided-isolation-of-antifungal-saponins-from-hosta-plantaginea-leaves
#19
Meng-Yue Wang, Ying Peng, Chong-Sheng Peng, Jiang-Yuan Qu, Xiao-Bo Li
Four new steroidal saponins hostaside Ⅰ (1), hostaside Ⅱ (2), hostaside Ⅲ (3), and hostaside Ⅳ (4), together with five known steroidal saponins (5-9), were isolated by the bioassay-guided fractionation from the leaves of Hosta plantaginea (Lam.) Aschers, a worldwide well-known ornamental plant. Hostasides Ⅰ and Ⅱ showed significant antifungal activities, and they could inhibit the growth of Candida albicans and Fusarium oxysporium with MIC values as low as 4 μg/ml.
May 23, 2017: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/28533240/heterocycle-thiazole-compounds-exhibit-antifungal-activity-through-increase-in-the-production-of-reactive-oxygen-species-in-cryptococcus-neoformans-cryptococcus-gattii-species-complex
#20
Nívea Pereira de Sá, Caroline Miranda de Lima, Cleudiomar Inácio Lino, Paulo Jorge Sanches Barbeira, Ludmila de Matos Baltazar, Daniel Assis Santos, Renata Barbosa de Oliveira, Eleftherios Mylonakis, Beth Burgwyn Fuchs, Susana Johann
Human cryptococcosis can occur as a primary or opportunistic infection and develops as an acute, sub-acute, or chronic systemic infection, involving different organs of the host. Given the limited therapeutic options and the occasional resistance to fluconazole, there is a need to develop novel drugs for the treatment of cryptococcosis. In this report, we describe promising thiazoles 1, 2, 3, and 4 and explore their possible modes of action against Cryptococcus. To this end, we show evidence of interference in the Cryptococcus antioxidant system...
May 22, 2017: Antimicrobial Agents and Chemotherapy
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